Cellular immunity to collagen and laminin in scleroderma

Huffstutter, J. Eugene; DeLustro, Frank; LeRoy, E. Carwile

doi:10.1002/art.1780280708

Cited by 42 publications

(23 citation statements)

References 23 publications

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“…In vitro studies have demonstrated that IL-4 induces the production of IL-6 in human skin fibroblasts [32], suggesting that these cytokines are able to amplify the stimulating effect of collagen synthesis on fibroblasts. Elevated IL-6 levels are also frequently found in the serum of patients with SSc [7]. Additionally, recent studies have indicated that IL-13 plays an important role in the pathogenesis of fibrosis [11, 12, 13, 14, 15, 16]due to its profibrotic effects.…”

Section: Discussionmentioning

confidence: 99%

“…IL-4 stimulates fibroblast proliferation, and fibroblast production in the extracellular matrix as well as myofibroblast differentiation [28, 29, 30]. Increased IL-4 production has been detected in the serum and in activated peripheral blood mononuclear cells of patients with SSc [7]. IL-6 has also been shown to stimulate the synthesis of collagen and glycosaminoglycans [31].…”

Section: Discussionmentioning

confidence: 99%

“…IL-4 is produced by activated memory T cells and mast cells, with both cell types playing a significant role in the pathogenesis of scleroderma. Increased IL-4 and IL-6 levels are detected in the serum of SSc patients [7]. …”

Section: Introductionmentioning

confidence: 99%

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Upregulation of Interleukin-13 and Its Receptor in a Murine Model of Bleomycin-Induced Scleroderma

Matsushita

Yamamoto

Nishioka³

2004

Int Arch Allergy Immunol

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Background: Interleukin-13 (IL-13) has been implicated in the pathogenesis of fibrotic conditions. Previously, a murine model for scleroderma has been established by repeated local injections of bleomycin. This animal model enabled us to study local expression and production of IL-13 in skin lesions during disease progression. Methods: Dermal sclerosis (DSc) was induced by repeated subcutaneous injections of bleomycin (1 mg/ml) in C3H/HeJ mice. IL-13 and IL-4 expressions were examined by RT-PCR, ELISA and immunohistochemistry. Results: RT-PCR showed that both IL-4 and IL-13 mRNA levels in skin lesions were increased and peaked after 4 weeks of bleomycin treatment. Quantification by densitometry revealed up to 4.2- and 1.9-fold increases, respectively. Immunohistochemical localization showed in skin lesions expression of IL-13 on infiltrating inflammatory cells, including mononuclear cells and possibly mast cells, increased with DSc progression. IL-13 protein production was also significantly increased. In skin lesions, IL-13 receptor (IL-13R) α2 expression was augmented mainly in the infiltrating mononuclear cells after 4 weeks of bleomycin exposure. IL-13Rα2, but not IL-13Rα1, mRNA was upregulated in the whole skin after 4 weeks. On the contrary, mRNA expression of IL-13Rα1 and IL- 13Rα2 was significantly altered in the cultured fibroblasts derived from bleomycin-treated skin. Conclusion: These data demonstrate that in skin lesions levels of IL-13 as well as its receptor increase in parallel with DSc progression, suggesting that IL-13 promotes the progression of cutaneous fibrosis/sclerosis in the murine model of bleomycin-induced scleroderma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Upregulation of Interleukin-13 and Its Receptor in a Murine Model of Bleomycin-Induced Scleroderma

Matsushita

Yamamoto

Nishioka³

2004

Int Arch Allergy Immunol

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“…In SSc patients serum antibodies and lymphocytes reactive with collagen have been found [2]. Autoimmunity to collagen has also been reported in primary Raynaud's phenomenon (PRP), a vasospastic disorder of the extremities consisting of an intermittent constriction of the small arterioles followed by venostasis and hyperaemia [3].…”

Section: Introductionmentioning

confidence: 99%

Anti-collagen antibodies in systemic sclerosis and in primary Raynaud's phenomenon

Riente

Marchini

Dolcher

et al. 1995

Clinical and Experimental Immunology

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SUMMARYThe frequency and specificity of antibodies to native and denatured coUagens were evaluated in systemic sclerosis (SSc) and in primary Raynaud's phenomenon (PRP) by direct and competitive ELISA. Antibodies reactive with denatured collagen type I (CI) were found in 43% of the SSc sera, and anti-CIV and anti-CV in 31%. In PRP, anti-CI, anti-CIV and anti-CV antibodies were detected in 8% of patient sera. Anti-CI, anti-CIV and anti-CV antibodies reacted with determinants expressed on the native as well as on the denatured molecule. Anti-CI and anti-CIV were cross-reactive; a reactivity with CII and a lower one with CV were detected. Anti-CV antibodies also reacted with CI and CII and, in a smaller proportion of cases, with CIV. Anti-collagen antibodies, affinity-purified from blotted collagen IV and V and cyanogen bromide (CBr)-digested CI, displayed the cross-reactivities shown by inhibition studies on sera. Moreover, antibodies eluted from a CBr fragment of CI reacted with the other CBr fragments as well. These data show that one-third of SSc sera contain antibodies that react with epitopes expressed on native as well as on heat-denatured CI, CII, CIV and CV, and therefore have the potential to bind collagens in vivo.

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“…IL-4, which is produced by activated memory T cells and mast cells, is known to promote fibroblast proliferation, collagen gene expression and collagen synthesis [78,79,80]. Plasma levels of IFN-γ are decreased in SSc patients, while those of IL-4, IL-10 and IL-13 are increased, compared with normal controls [81,82,83]. Serum in the majority of SSc patients showed elevated levels of CD30 [84], which is expressed on activated Th2-type cells.…”

Section: Roles Of Chemokines and Chemokine Receptors In Human Sclerodmentioning

confidence: 99%

Chemokines and Chemokine Receptors in Scleroderma

Yamamoto

2006

Int Arch Allergy Immunol

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Scleroderma is a connective tissue disease with unknown etiology characterized by excessive deposition of extracellular matrix in the skin. Cellular infiltrates of certain immune cells and proinflammatory mediators are suggested to play a crucial role in cutaneous fibrosis, forming complicated networks between fibroblasts and immune cells via cell-cell communications. Tissue-selective trafficking of leukocytes is mediated by combinations of adhesion molecules and chemokines. Recent studies have shown that an increase in proinflammatory chemokines has been associated with the initiation and/or development of skin fibrosis/sclerosis, suggesting that chemokines and their receptors may be important mediators of inflammation and fibrosis in scleroderma. This review will focus on the roles of chemokines and their receptors during the process of cutaneous sclerosis and will also provide a current insight into the potential mechanisms of scleroderma.

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Cellular immunity to collagen and laminin in scleroderma

Cited by 42 publications

References 23 publications

Upregulation of Interleukin-13 and Its Receptor in a Murine Model of Bleomycin-Induced Scleroderma

Upregulation of Interleukin-13 and Its Receptor in a Murine Model of Bleomycin-Induced Scleroderma

Anti-collagen antibodies in systemic sclerosis and in primary Raynaud's phenomenon

Chemokines and Chemokine Receptors in Scleroderma

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