Fibroblast proliferation

In mouse models of skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), there is a close association between elevated XO activity in the epidermis and hyperplasia (Pence and Reiners, 1987). This association is also seen in psoriasis patients (Eisen and Seegmiller, 1961 Zimmer and Demis, 1966 Kizaki et al., 1977). In the study by Kizaki etal. (1977), the epidermis was increased about five-fold in comparison to normal. It is not known whether XO-derived ROS have any role in psoriatic epidermal hyperproliferation but low levels of hydrogen peroxide added to the culture medium are well known to induce skin fibroblast proliferation in vitro, an eflfect that is greatest at low passage numbers (Murrell et al., 1990). The generation of... 

Mycobacterium avium infection DBA/lj T Hyperplasia, synovitis, synovial cyst formation, fibroblast proliferation, and osteoid deposition. Presence of neutrophils in the interarticular space. Higher levels of anti-CII Abs of the IgGl subtype. 93... 

Inhibition of IFN-y entails inhibition of fibroblast proliferation and differentiation, subsequent collagen synthesis, and increased expression of MMP-1 to promote degradation of matrix (105). IFN-y also triggers robust T-lymphocyte... 

Kwon BS, Wang S, Udagawa N, Haridas V, Lee ZH, Kim KK, Oh KO, Greene J, Li Y, Su J, Gentz R, Aggarwal BB, Ni J (1998) TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption. FASEB J 12 845-854... 

Toxicology. Paraquat is an irritant of the eyes, mucous membranes, and skin ingestion causes fibroblastic proliferation in the lungs. 

Fibroblasts and connective Poor wound healing and Impair fibroblast proliferation and collagen... 

TNF-a and IL-1 are current targets of antiinflammatory drug therapy. A homotrimer of 17-kDa protein subunits whose effects include the activation of neutrophils and eosinophils, induction of COX-2, induction of proinflammatory cytokines (e.g., IL-1, IL-6), enhancement of endothelial layer permeabihty, induction of adhesion molecules by endothelial cells and leukocytes, stimulation of fibroblast proliferation, degradation of cartilage, and stimulation of bone reabsorption. Two receptors mediate these effects a 55-kDa receptor (p55) and a 75-kDa receptor (p75). Each of these receptors is found in both cell surface and soluble forms. The binding of two or three cell surface receptors to TNF-a initiates an inflammatory response. Soluble p55 also acts as a signaling receptor for inflammatory responses, whereas soluble p75 acts as an antagonist. 

Penicillamine (Cuprimine) can be used to treat acute, severe rheumatoid arthritis, producing reductions in joint pain, edema, and stiffness. The response to penicillamine is usually delayed (4-12 weeks), and remissions can last several months after withdrawal of treatment. Radiographic evidence of this drug s efficacy is limited thus, penicillamine is seldom used to treat rheumatoid arthritis. The mechanism of action of penicillamine is unknown, but some evidence suggests that it may involve the inhibition of angiogenesis, synovial fibroblast proliferation, or transcriptional activation. Because penicillamine can chelate copper and promote its excretion, it is used to treat Wilson s disease (hepatolenticular degeneration) and has also been used in mercury and lead intoxication. 

C12. Chiou, G. C., Xuan, B., Liu, Q., Yamasaki, T., and Okawara, T., Inhibition of interleukin-1-induced uveitis and corneal fibroblast proliferation by interleukin-1 blockers. J. Ocul. Pharmacol. Ther. 16, 407-418 (2000). 

Byun, J. H., Huh, J. E., Park, S. J. et al. (2000). Myocardial injury-induced fibroblast proliferation facilitates retroviral-mediated gene transfer to the rat heart in vivo. J. Gene Med. 2(1), 2-10. 

Olson, E.R., Naugle, J.E., Zhang, X., Bomser, J.A., and Meszaros, J.G. 2005. Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol. Am. J. Physiol. 288 H1131-H1138. 

Topical dexpanthenol, a stable alcoholic analog of pantothenic acid with good skin penetration, acts like a moisturizer, improves stratum corneum hydration, reduces transepidermal water loss, and maintains skin softness and elasticity. In wound-healing activation of fibroblast proliferation has been observed in vitro and in vivo with dexpanthenol concomitantly with increased elastic and solid tissue regeneration. In skin irritation pretreatment with dexpanthenol resulted in less damage to the stratum corneum barrier, while adjuvant treatment improved the symptoms of dryness, roughness, scaling pruritus, erythema, and erosions considerably. The topical application is well-tolerated with a minimal risk of skin irritation or sensitization.129-132... 

Figure 27.19. Illustration of early asbestos-induced fibroproliferative lesions in a rat inhalation model. (1) Inhaled fibers deposit at alveolar duct bifurcations. (2) Within 24 hr, macrophages accumulate at sites of fiber deposition and become activated by fibers to secrete growth factors. (3) Within 72hr fibroblasts proliferate.

Inhibits TGF-02-induced synovial fibroblast proliferation [AI, anti-proliferative] Ser/ThrPK receptor... 

A sublibrary L17, made of 42 diverse library individuals (Fig. 11.23), was screened in an in vivo model for the proliferation of fibroblasts, where a high value represented a candidate for the tissue reconstruction process around the medical implant. The screening protocol was performed in parallel, and a correlation was established between the fibroblast proliferation (biological property) and the air-water contact angle (physicochemical property). A crude SAR was assessed for further, more... 

Evidence indicates that steroids affect other cells and substances that modulate inflammation. Exposure of human basophils to steroid in culture inhibits histamine release induced by an IgE-dependent stimulus. Steroids inhibit phospholipase A2, which prevents biosynthesis of arachidonic acid and subsequent formation of prostacyclin, thromboxane A, prostaglandins, and leukotrienes. Steroids also decrease capillary permeability and fibroblast proliferation and the quantity of collagen deposition, thereby influencing tissue regeneration and repair. 

In severe refractory cases of VKC, treatment options include surgical excision of the giant papillae and cryotherapy of the upper tarsus. Improvement is limited, however, and scarring may result. Supratarsal steroid injection is another treatment option. Symptomatic relief takes place in 1 to 5 days, giant papillae decrease in 5 to 17 days, and shield ulcers resolve in 12 to 20 days. After injection, patients are maintained on conventional treatment modalities. Mitomycin C, which inhibits inflammatory cells and fibroblast proliferation, has been found to alleviate the signs and symptoms of severe refractory cases. Anmiotic membranes are another treatment consideration for severe cases. 

The mechanism of action of talc in pleurodesis has not been fully elucidated, although it is thought to stimulate a typical local inflammatory response, with reduced fibrinolytic activity, mesothelial cell injury, and fibroblast proliferation. Pneumonitis or respiratory failure can be secondary to downstream inflammatory mediators from more proximal talc injury (7). This acute-phase inflammatory response is dose-related (8,9) and is inhibited by glucocorticoids (10). Talc may also have an adhesion stimulating quality, since empyema alone stimulates a typical inflammatory response but does not lead to pleurodesis (11). In fact, talc stimulates intercellular adhesion molecule-1 in mesothelial cells (12). The mechanism of chronic fibrosis may involve continuous fibroblast activation by foreign body giant cell released mediators or macrophages. 

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