Fibrotic responses

CysLT2 ltc4/ltd4 lte4 Gq tPLC, tCa2+ 4- Pulmonary inflammatory and fibrotic response... 

TGF-p has been thought to be an important cytokine in mediating fibrotic responses during normal wound healing in many tissues. Upon injury, TGF-pi is... 

Leask A, Abraham DJ. TGF-P signaling and the fibrotic response. Journal of the Federation of American Societies for Experimental Biology 2004, 18, 816-827. 

Carbon nanotubes (CNTs) currently attract intense interest because of their unique properties which make them suitable for many industrial applications.28 Carbon nanotubes exhibit some of the properties implied in asbestos toxicity. Carbon nanotubes share with asbestos the fibrous habit - long fibers with a diameter of a few nanometers -and a very high biopersistence. On this basis they are suspected to be hazardous and indeed the first studies in vivo14,29,30 have shown an inflammatory response followed by some evolution towards fibrosis. When inhaled, CNTs may thus constitute a possible hazard to human health. The inflammatory and fibrotic responses elicited by CNTs is similar to that caused by other toxic particles which might be the result of oxidative stress caused by particle- and/or cell-derived free radicals. There is no direct experimental evidence of a capacity of carbon nanotubes to generate free radicals similar to silica asbestos and nano sized iron oxide particles. 

Thermosensitive block copolymer nanoparticles containing doxorubicin increased cytotoxicity against Lewis lung carcinoma cells when activated by heating above the LCST [139], Chitosan was chemically conjugated to NIPAAm/vinyl laurate copolymer to enhance gene transfection in mouse myoblast cells [140]. Upon i.v. administration, poly(NIPAAm) nanoparticles are taken up by the reticuloendothelial cells of the liver and mild inflammatory and fibrotic responses are observed... 

Fihrogenic—Causing or contributing to the fibrotic response mechanism in tissues commonly refers to substances that contribute to fibrosis of the lungs or liver. 

As mast cells are normally found in skin, this recruitment of mast cells may simply reflect the restoration of normal tissue homeostasis, although they may play an intermediate role. Mast cells are also found in keloids and hypertrophic scars (Smith etal., 1987), both of which are considered to be abnormal typ>es of wound healing, and it has been su ested that this provides further evidence of their involvement in fibrotic responses. 

A number of acute and chronic manifestations of histoplasmosis appear to resnlt from nnnsnal inflammatory or fibrotic responses to the pathogen, inclnding pericarditis and rheumatologic syndromes during the first year after exposnre, with chronic mediastinal inflammation or fibrosis, broncholithiasis, and enlarging parenchymal granulomas later in the course of disease. 

HCV has been associated with many extrahepatic manifestations [35, 36, 67], including myocarditis and cardiomyopathy [68, 69]. Histological and functional observations have led to the hypothesis that mast cells play an important role in many fibrotic reactions [70-72], Potential mast cell-derived mediators of the fibrotic response include histamine, tryptase and TGF-fl, which stimulate fibroblast proliferation and collagen synthesis [73-75]. By producing these factors, chronic activation of cardiac mast cells by protein Fv may contribute to the heart fibrosis found in some patients with HCV infection [68, 69]. 

Kolb M, Margetts PJ, Galt T, Sime PJ, Xing Z, Schmidt M, Gauldie J. Transient transgene expression of decorin in the lung reduces the fibrotic response to bleomycin. Am J Respir Crit Care Med 2001 163 770-777. 

Although not all inflammatory disorders result in fibrosis, fibrotic responses are always preceded and potentially perpetuated by chronic inflammation. The salient feature of chronic inflammation is the association of leukocyte infiltration. These recruited leukocytes contribute to the pathogenesis of chronic inflammation, and promote fibrosis via the elaboration of a variety of cytokines. The maintenance of leukocyte recruitment during inflammation requires intercellular communication between infiltrating leukocytes and the endothelium, resident stromal cells, and parenchymal cells. These events are mediated via the generation of early response cytokines, e.g., IL-1 and TNF, the expression of cell surface adhesion molecules, and the production of chemotactic molecules, such as chemo-kines. 

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