共查询到20条相似文献,搜索用时 15 毫秒
1.
Marta Michalik Katarzyna Wójcik-Pszczoła Milena Paw Dawid Wnuk Paulina Koczurkiewicz Marek Sanak Elżbieta Pękala Zbigniew Madeja 《Cellular and molecular life sciences : CMLS》2018,75(21):3943-3961
Bronchial asthma is a chronic inflammatory disease in which bronchial wall remodelling plays a significant role. This phenomenon is related to enhanced proliferation of airway smooth muscle cells, elevated extracellular matrix protein secretion and an increased number of myofibroblasts. Phenotypic fibroblast-to-myofibroblast transition represents one of the primary mechanisms by which myofibroblasts arise in fibrotic lung tissue. Fibroblast-to-myofibroblast transition requires a combination of several types of factors, the most important of which are divided into humoural and mechanical factors, as well as certain extracellular matrix proteins. Despite intensive research on the nature of this process, its underlying mechanisms during bronchial airway wall remodelling in asthma are not yet fully clarified. This review focuses on what is known about the nature of fibroblast-to-myofibroblast transition in asthma. We aim to consider possible mechanisms and conditions that may play an important role in fibroblast-to-myofibroblast transition but have not yet been discussed in this context. Recent studies have shown that some inherent and previously undescribed features of fibroblasts can also play a significant role in fibroblast-to-myofibroblast transition. Differences observed between asthmatic and non-asthmatic bronchial fibroblasts (e.g., response to transforming growth factor β, cell shape, elasticity, and protein expression profile) may have a crucial influence on this phenomenon. An accurate understanding and recognition of all factors affecting fibroblast-to-myofibroblast transition might provide an opportunity to discover efficient methods of counteracting this phenomenon. 相似文献
2.
Leukotrienes: Mediators that have been typecast as villains 总被引:2,自引:0,他引:2
Flamand N Mancuso P Serezani CH Brock TG 《Cellular and molecular life sciences : CMLS》2007,64(19-20):2657-2670
As befalls many mediators that act upon the human stage, leukotrienes have become identified with their most powerful roles as villains of the immune system. They are well known for their leading roles in allergic diseases, including asthma. They also have gained recognition for their dramatic role as promoters of inflammation. As new roles for these lipid messengers are sought, it is becoming apparent that the leukotrienes have been typecast as bad guys of the immune system. As examples, their more recent roles have been in atherosclerosis, pulmonary fibrosis and cancer. However, upon further evaluation, we can begin to see their versatility. Thus, leukotrienes stimulate innate immunity against pathogens. In addition, they promote the expression of mediators, receptors and other molecules that are important for immune defense. In these lesser known roles, they lead the fight against bacterial, fungal and viral infection. This review is intended to shed light on the leukotrienes, where they come from and what we really know about them. 相似文献
3.
Luschnig-Schratl P Sturm EM Konya V Philipose S Marsche G Fröhlich E Samberger C Lang-Loidolt D Gattenlöhner S Lippe IT Peskar BA Schuligoi R Heinemann A 《Cellular and molecular life sciences : CMLS》2011,68(21):3573-3587
Accumulation of eosinophils in tissue is a hallmark of allergic inflammation. Here we observed that a selective agonist of the PGE2 receptor EP4, ONO AE1-329, potently attenuated the chemotaxis of human peripheral blood eosinophils, upregulation of the adhesion molecule CD11b and the production of reactive oxygen species. These effects were accompanied by the inhibition of cytoskeletal rearrangement and Ca2+ mobilization. The involvement of the EP4 receptor was substantiated by a selective EP4 antagonist, which reversed the inhibitory effects of PGE2 and the EP4 agonist. Selective kinase inhibitors revealed that the inhibitory effect of EP4 stimulation on eosinophil migration depended upon activation of PI 3-kinase and PKC, but not cAMP. Finally, we found that EP4 receptors are expressed by human eosinophils, and are also present on infiltrating leukocytes in inflamed human nasal mucosa. These data indicate that EP4 agonists might be a novel therapeutic option in eosinophilic diseases. 相似文献
4.
David N. O’Dwyer Bethany B. Moore 《Cellular and molecular life sciences : CMLS》2017,74(23):4305-4314
Periostin is a protein that plays a key role in development and repair within the biological matrix of the lung. As a matricellular protein that does not contribute to extracellular matrix structure, periostin interacts with other extracellular matrix proteins to regulate the composition of the matrix in the lung and other organs. In this review, we discuss the studies exploring the role of periostin to date in chronic respiratory diseases, namely asthma and idiopathic pulmonary fibrosis. Asthma is a major health problem globally affecting millions of people worldwide with significant associated morbidity and mortality. Periostin is highly expressed in the lungs of asthmatic patients, contributes to mucus secretion, airway fibrosis and remodeling and is recognized as a biomarker of Th2 high inflammation. Idiopathic pulmonary fibrosis is a fatal interstitial lung disease characterized by progressive aberrant fibrosis of the lung matrix and respiratory failure. It predominantly affects adults over 50 years of age and its incidence is increasing worldwide. Periostin is also highly expressed in the lungs of idiopathic pulmonary fibrosis patients. Serum levels of periostin may predict clinical progression in this disease and periostin promotes myofibroblast differentiation and type 1 collagen production to contribute to aberrant lung fibrosis. Studies to date suggest that periostin is a key player in several pathogenic mechanisms within the lung and may provide us with a useful biomarker of clinical progression in both asthma and idiopathic pulmonary fibrosis. 相似文献
5.
Navarro S Aleu J Jiménez M Boix E Cuchillo CM Nogués MV 《Cellular and molecular life sciences : CMLS》2008,65(2):324-337
Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated
eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this
work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation
to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization
of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation,
reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually,
cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed.
In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and
may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present.
Received 26 October 2007; accepted 23 November 2007 相似文献
6.
Regulatory mechanisms of mitogen-activated kinase signaling 总被引:5,自引:1,他引:4
MAP kinases (MAPKs) are evolutionarily conserved regulators that mediate signal transduction and play essential roles in various
physiological processes. There are three main families of MAPKs in mammals, whose functions are regulated by activators, inactivators,
substrates and scaffolds, which together form delicate signaling cascades in response to different extracellular or intracellular
stimulation. MAPK signaling is tightly regulated so that optimal biological activities are achieved and health is maintained.
However, how the specificity of the signaling flow along each cascade is achieved is still relatively unclear. In this review,
we summarize recent advances in understanding the regulation of MAPK cascades and the roles of MAP kinases and their regulators
in development and in immune responses.
Received 11 January 2007; received after revision 31 May 2007; accepted 5 July 2007 相似文献
7.
Immune responses to DNA vaccines 总被引:16,自引:0,他引:16
DNA vaccines, based on plasmid vectors expressing an antigen under the control of a strong promoter, have been shown to induce
protective immune responses to a number of pathogens, including viruses, bacteria and parasites. They have also displayed
efficacy in treatment or prevention of cancer, allergic diseases and autoimmunity. Immunologically, DNA vaccines induce a
full spectrum of immune responses that include cytolytic T cells, T helper cells and antibodies. The immune response to DNA
vaccines can be enhanced by genetic engineering of the antigen to facilitate its presentation to B and T cells. Furthermore,
the immune response can be modulated by genetic adjuvants in the form of vectors expressing biologically active determinants
or by more traditional adjuvants that facilitate uptake of DNA into cells. The ease of genetic manipulation of DNA vaccines
invites their use not only as vaccines but also as research tools for immunologists and microbiologists.
Received 26 October 1998; received after revision 3 December 1998; accepted 3 December 1998 相似文献
8.
Helan Xiao Debbie X. Li Mingyao Liu 《Cellular and molecular life sciences : CMLS》2012,69(24):4149-4162
Airway epithelial cell migration is essential for lung development and growth, as well as the maintenance of respiratory tissue integrity. This vital cellular process is also important for the repair and regeneration of damaged airway epithelium. More importantly, several lung diseases characterized by aberrant tissue remodeling result from the improper repair of damaged respiratory tissue. Epithelial cell migration relies upon extracellular matrix molecules and is further regulated by numerous local, neuronal, and hormonal factors. Under inflammatory conditions, cell migration can also be stimulated by certain cytokines and chemokines. Many well-known environmental factors involved in the pathogenesis of chronic lung diseases (e.g., cigarette smoking, air pollution, alcohol intake, inflammation, viral and bacterial infections) can inhibit airway epithelial cell migration. Further investigation of cellular and molecular mechanisms of cell migration with advanced techniques may provide knowledge that is relevant to physiological and pathological conditions. These studies may eventually lead to the development of therapeutic interventions to improve lung repair and regeneration and to prevent aberrant remodeling in the lung. 相似文献
9.
Tsatsanis C Dermitzaki E Venihaki M Chatzaki E Minas V Gravanis A Margioris AN 《Cellular and molecular life sciences : CMLS》2007,64(13):1638-1655
Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator
of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal
gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal
(HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests
that CRF and its related peptides also affect the adrenals directly, i.e. not through the CNS but from within the adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its related
peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF type 1 (CRF1) and 2 (CRF2) as well as the endogenous pseudo-receptor CRF-binding protein (CRF-BP) are all expressed in adrenal cortical, medullary
chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory system is complex and depends on the balance
between the local concentration of CRF ligands and the availability of their receptors.
Received 19 December 2006; received after revision 20 February 2007; accepted 26 March 2007 相似文献
10.
Rosenstiel P Jacobs G Till A Schreiber S 《Cellular and molecular life sciences : CMLS》2008,65(9):1361-1377
NOD-like receptors (NLRs) comprise a family of cytosolic proteins that have been implicated as ancient cellular sentinels
mediating protective immune responses elicited by intracellular pathogens or endogenous danger signals. Genetic variants in
NLR genes have been associated with complex chronic inflammatory barrier diseases (e.g. Crohn disease, bronchial asthma). In
this review, we focus on the molecular pathophysiology of NLRs in the context of chronic inflammatory diseases and pinpoint
recent advances in the evolutionary understanding of NLR biology. We propose that the field of NLRs may serve as a prototype
for how a comprehensive understanding of an element of the immunological barrier will eventually lead to the development of
targeted diagnostic, therapeutic and/or preventive strategies.
Received 29 October 2007; received after revision 10 December 2007; accepted 19 December 2007 相似文献
11.
Kenji Izuhara Satoshi Nunomura Yasuhiro Nanri Masahiro Ogawa Junya Ono Yasutaka Mitamura Tomohito Yoshihara 《Cellular and molecular life sciences : CMLS》2017,74(23):4293-4303
We found for the first time that IL-4 and IL-13, signature type 2 cytokines, are able to induce periostin expression. We and others have subsequently shown that periostin is highly expressed in chronic inflammatory diseases―asthma, atopic dermatitis, eosinophilc chronic sinusitis/chronic rhinosinusitis with nasal polyp, and allergic conjunctivitis—and that periostin plays important roles in the pathogenesis of these diseases. The epithelial/mesenchymal interaction via periostin is important for the onset of allergic inflammation, in which periostin derived from fibroblasts acts on epithelial cells or fibroblasts, activating their NF-κB. Moreover, the immune cell/non-immune cell interaction via periostin may be also involved. Now the significance of periostin has been expanded into other inflammatory or fibrotic diseases such as scleroderma and pulmonary fibrosis. The cross-talk of periostin with TGF-β or pro-inflammatory cytokines is important for the underlying mechanism of these diseases. Because of its pathogenic importance and broad expression, diagnostics or therapeutic drugs can be potentially developed to target periostin as a means of treating these diseases. 相似文献
12.
de Wit PJ 《Cellular and molecular life sciences : CMLS》2007,64(21):2726-2732
Plants have an innate immunity system to defend themselves against pathogens. With the primary immune system, plants recognize
microbe-associated molecular patterns (MAMPs) of potential pathogens through pattern recognition receptors (PRRs) that mediate
a basal defense response. Plant pathogens suppress this basal defense response by means of effectors that enable them to cause
disease. With the secondary immune system, plants have gained the ability to recognize effector-induced perturbations of host
targets through resistance proteins (RPs) that mediate a strong local defense response that stops pathogen growth. Both primary
and secondary immune responses in plants depend on germ line-encoded PRRs and RPs. During induction of local immune responses,
systemic immune responses also become activated, which predispose plants to become more resistant to subsequent pathogen attacks.
This review gives an update on recent findings that have enhanced our understanding of plant innate immunity and the arms
race between plants and their pathogens.
Received 24 June 2007; received after revision 18 July 2007; accepted 15 August 2007 相似文献
13.
The innate immunity of the central nervous system in chronic pain: The role of Toll-like receptors 总被引:1,自引:0,他引:1
Toll-like receptors (TLRs) are a family of pattern recognition receptors that mediate innate immune responses to stimuli from
pathogens or endogenous signals. Under various pathological conditions, the central nervous system (CNS) mounts a well-organized
innate immune response, in which glial cells, in particular microglia, are activated. Further, the innate immune system has
emerged as a promising target for therapeutic control of development and persistence of chronic pain. Especially, microglial
cells respond to peripheral and central infection, injury, and other stressor signals arriving at the CNS and initiate a CNS
immune activation that might contribute to chronic pain facilitation. In the orchestration of this limited immune reaction,
TLRs on microglia appear to be most relevant in triggering and tailoring microglial activation, which might be a driving force
of chronic pain. New therapeutic approaches targeting the CNS innate immune system may achieve the essential pharmacological
control of chronic pain.
Received 21 November 2006; received after revision 8 January 2007; accepted 7 February 2007 相似文献
14.
P. J. Barnes 《Cellular and molecular life sciences : CMLS》1987,43(7):833-839
Summary Many regulatory peptides have been described in the respiratory tract of animals and humans. Some peptides (bombesin, calcitonin, calcitonin gene-related peptide) are localised to neuroendocrine cells and may have a trophic or transmitter role. Others are localised to motor nerves. Vasoactive intestinal peptide and peptide histidine isoleucine are candidates for neurotransmitters of non-adrenergic inhibitory fibres and may be cotransmitters in cholinergic nerves. These peptides may regulate airway smooth muscle tone, bronchial blood flow and airway secretions. Sensory neuropeptides (substance P, neurokinin A and B, calcitonin gene-related peptide) may contract airway smooth muscle, stimulate mucus secretion and regulate bronchial blood flow and microvascular permeability. If released by an axon reflex mechanism these peptides may be involved in the pathogenesis of asthma. Other peptides, such as galanin and neuropeptide Y, are also present but their function is not yet known. 相似文献
15.
Regulatory peptides in the respiratory system 总被引:2,自引:0,他引:2
P J Barnes 《Experientia》1987,43(7):832-839
Many regulatory peptides have been described in the respiratory tract of animals and humans. Some peptides (bombesin, calcitonin, calcitonin gene-related peptide) are localised to neuroendocrine cells and may have a trophic or transmitter role. Others are localised to motor nerves. Vasoactive intestinal peptide and peptide histidine isoleucine are candidates for neurotransmitters of non-adrenergic inhibitory fibres and may be cotransmitters in cholinergic nerves. These peptides may regulate airway smooth muscle tone, bronchial blood flow and airway secretions. Sensory neuropeptides (substance P, neurokinin A and B, calcitonin gene-related peptide) may contract airway smooth muscle, stimulate mucus secretion and regulate bronchial blood flow and microvascular permeability. If released by an axon reflex mechanism these peptides may be involved in the pathogenesis of asthma. Other peptides, such as galanin and neuropeptide Y, are also present but their function is not yet known. 相似文献
16.
Marsh LM Pfefferle PI Pinkenburg O Renz H 《Cellular and molecular life sciences : CMLS》2011,68(11):1851-1862
Allergy and asthma are chronic inflammatory diseases which result from complex gene–environment interactions. Recent evidence
indicates the importance of prenatal and postnatal developmental processes in terms of maturation of balanced immune responses.
According to the current view, gene–environment interactions during a restricted time frame are responsible for programming
of the immune system in favor of allergic immune mechanisms later in life. The interaction between genes and environment is
complex and only partially understood; however, heritable epigenetic modifications including chemical additions in and alternative
packaging of the DNA have been shown to play a crucial role in this context. Novel data indicate that epigenetic mechanisms
contribute to the development of T-helper cell function. Environmental factors, including diesel exhaust particles (DEP),
vitamins and tobacco smoke, operate through such mechanisms. Furthermore, the role of environmental microbes provides another
and maybe even more important group of exogenous exposures which operates in this critical time frame. 相似文献
17.
Towards progress on DNA vaccines for cancer 总被引:2,自引:0,他引:2
Lowe DB Shearer MH Jumper CA Kennedy RC 《Cellular and molecular life sciences : CMLS》2007,64(18):2391-2403
Cancer immunotherapy faces many obstacles that include eliciting immune reactions to self antigens as well as overcoming tumor-derived
immunosuppressive networks and evasion tactics. Within the vaccine arsenal for inhibiting cancer proliferation, plasmid DNA
represents a novel immunization strategy that is capable of eliciting both humoral and cellular arms of the immune response
in addition to being safely administered and easily engineered and manufactured. Unfortunately, while DNA vaccines have performed
well in preventing and treating malignancies in animal models, their overall application in human clinical trials has not
impacted cancer regression to date. Since the establishment of these early trials, progress has been made in terms of increasing
DNA vaccine immunogenicity and subverting the suppressive properties of tumor cells. Therefore, the success of future plasmid
DNA use in cancer patients will depend on combinatorial strategies that enhance and direct the DNA vaccine immune response
while also targeting tumor evasion mechanisms.
Received 2 April 2007; received after revision 14 May 2007; accepted 21 May 2007 相似文献
18.
Mangoni ML 《Cellular and molecular life sciences : CMLS》2011,68(13):2157-2159
Primitive innate defense mechanisms in the form of gene-encoded antimicrobial peptides are now considered as potential candidates
for the development of new therapeutics. They are well known for their function as the first protective barrier of all organisms
against microbial infections. In addition, emerging studies reveal that they assist in modulating the host immune system.
The biological properties of these host-defense peptides, their role in human health, their cell selectivity and related molecular
mechanisms are discussed in this multi-author review along with the strategies to transform them or their peptidomimetics
into clinically usable drugs. 相似文献
19.
L. P. Bignold 《Cellular and molecular life sciences : CMLS》1995,51(4):317-327
Eosinophil leukocytes have been studied for over 100 years, with various theories being advanced of the mechanism of their recruitment and function, especially in relation to the lesions of allergy, asthma and parasitism. Early notions of recruitment and function depended on observations of the cells in inflammatory lesions, while later theories have used additional information from in vitro studies. Many issues are still unresolved. This review aims to cover the older and more recent literature of the mechanisms of accumulation of eosinophil leukocytes and their functions, with a view to illuminating the controversies and difficulties of research in the area. 相似文献
20.
Integrin antagonists 总被引:4,自引:0,他引:4
Integrins are a family of cell surface glycoproteins that mediate numerous cell-cell and cell-matrix interactions and are
involved in biological processes such as tissue morphogenesis, leukocyte recirculation and migration, wound healing, blood
clotting and immune response. Aberrant cell adhesion has been implicated in the pathogenesis of several diseases, including
a number of inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease and asthma, as well as cancer
and coronary heart disease. As such integrins are seen as excellent targets for the development of therapeutic agents. This
report begins with an examination of the structure of integrin molecules and their ligands and then goes on to review the
current state of development of antiintegrin antagonists.
Received 13 April 1999; received after revision 28 May 1999; accepted 28 May 1999 相似文献