SKL-2841, a dual antagonist of MCP-1 and MIP-1 beta, prevents bleomycin-induced skin sclerosis in mice

Kimura, Mizuho; Kawahito, Yutaka; Hamaguchi, Masahide; Nakamura, Takashi; Okamoto, Masayuki; Matsumoto, Yohei; Endo, Hirahito; Yamamoto, Aihiro; Ishino, H.; Wada, Makoto; Omoto, Atsushi; Tsubouchi, Yasunori; Kohno, Masataka; Yoshikawa, Toshikazu

doi:10.1016/j.biopha.2006.10.002

Cited by 22 publications

(14 citation statements)

References 21 publications

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“…As tested here for SSc patients, CCL2 concentrations were found to be correlated with lung-function parameters and HR-CT score. The importance of CCL2 as a key mediator for lung fibrosis also is supported by data from animal models showing a reduction and prevention of bleomycin-induced lung fibrosis by anti-CCL2 monoclonal antibodies or by pharmacologic blockade, respectively [ 22 , 23 ]. CCL2 also mediates profibrotic effects in SSc through the release of IL-4 from T cells, and IL-4 also was found to correlate with lung-function parameters in our study [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients

et al. 2009

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“…They show that the loss of CCL2 significantly alters the assembly and accumulation of collagen. Another study showed that intraperitoneal administration of SKL-2841, an antagonist of CCL2, reduced the infiltration of inflammatory mononuclear cells and polymorphonuclear cells and also significantly suppressed fibrillization in bleomycin-induced scleroderma (119). These studies suggest that blockade of CCL2 may abrogate skin sclerosis, which might lead to the therapeutic potential.…”

Section: Therapeutic Strategiesmentioning

confidence: 90%

Pathogenic role of CCL2/MCP-1 in scleroderma

Yamamoto¹

2008

Front Biosci

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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 fibrotic condition, suggesting that chemokines and their receptors may be important mediators of inflammation and fibrosis in scleroderma. In particular, CCL2/monocyte chemoattractant protein-1 (MCP-1) has been suggested to play an important role in scleroderma. This review will focus on the roles of CCL2 and its receptor during the process of cutaneous sclerosis, and also provide a current insight into the potential mechanisms of scleroderma.

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“…SKL-2841 is a compound with antichemotactic properties against MCP-1 and MIP-1 beta. When administered intraperitonealy to bleomycin-treated mice, this compound significantly reduced the inflammatory skin infiltration in the acute phase and the dermal sclerosis seen in the chronic phase, compared to controls [203]. Intramuscular administration of the IL-12 encoding plasmid (pCAGGSIL-12) to the tight-skin mouse model of SSc significantly decreased skin thickness as well as the levels of autoantibodies and the production of IL-4 from splenocytes of treated mice [204].…”

Section: Treatments Targeting Fibrosismentioning

confidence: 96%

Recent Advances in the Treatment of Systemic Sclerosis

Bournia

Vlachoyiannopoulos

Selmi

et al. 2009

Clinic Rev Allerg Immunol

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Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. The involvement of internal organs results in significant morbidity and mortality of SSc patients with cardiopulmonary involvement being the leading cause of SSc-related deaths. The management of SSc patients remains a challenge because therapeutic options are rather limited and no therapy has definitively shown a disease-modifying effect. A significant progress that has recently been made in the understanding of the SSc pathogenesis contributed to the introduction of new therapeutic options. Preliminary clinical studies have yielded promising results for mycophenolate mofetil, anti-CD20 antibodies, and stem-cell in the treatment of SSc. Multicenter cohort studies help understand the natural history of SSc, which leads to improvement in the care of SSc patients. The major objective of those studies is to establish the screening strategies for early diagnosis and, subsequently, to introduce appropriate management concerning specific organ involvement in SSc as well as to formulate specific treatment recommendations.

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SKL-2841, a dual antagonist of MCP-1 and MIP-1 beta, prevents bleomycin-induced skin sclerosis in mice

Cited by 22 publications

References 21 publications

Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients

Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients

Pathogenic role of CCL2/MCP-1 in scleroderma

Recent Advances in the Treatment of Systemic Sclerosis

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