دانلود رایگان مقاله سلول دندریتیک - رزیگلیتازون با بهبود آرتریت - کلاژن

abstract

Rosiglitazone is a selective ligand for peroxisome proliferator-activated receptor-gamma (PPAR-c), which serves diverse biological functions. A number of autoimmune disease models have been used to examine the anti-inflammatory and immunosuppressive effects of tolerogenic dendritic cells (tDCs). The aim of the present study was to investigate whether rosiglitazone-mediated DC (Rosi-DC) therapy suppressed arthritis in a collagen-induced arthritis (CIA) mouse model. Rosi-DCs were generated by treating immature DCs with TNF-a, type II collagen, and rosiglitazone. CIA mice then received subcutaneously (s.c.) two injections of Rosi-DCs. The severity of arthritis was then assessed histopathologically. The phenotypes of the DC and regulatory T (Treg) cell populations in CIA mice were determined by flow cytometry and the effect of Rosi-DCs on the secretion of autoimmunity-inducing cytokines was examined by ELISA. Rosi-DCs expressed lower levels of DC-related surface markers than mature DCs. Histopathological examination revealed that the degree of inflammation in the paws of Rosi-DC-treated mice was much lower than that in the paws of PBS-treated CIA mice. Taken together, these results clearly show that rosiglitazone-mediated DCs ameliorate CIA, most likely via the induction of antigen-specific Treg cells.

4. Discussion

PPARs are ligand activated transcription factors belonging to the nuclear hormone receptor superfamily, which includes the classic steroid, thyroid, and retinoid hormone receptors as well as many orphan receptors [17]. The three members of the PPAR subfamily are PPAR-a, PPAR-c, and PPAR-b/d. PPAR-a is expressed mainly in the liver, whereas PPAR-c is expressed in adipose tissue, macrophages, and DCs; PPAR-b/d is ubiquitously expressed [18]. The phenotype and functional heterogeneity of DCs primarily stems from the diverse tissue microenvironments in which they reside. Changes in the local tissue environment alter the extracellular lipid milieu, which in turn modifies intracellular lipid metabolism. Nuclear receptors receive extracellular and intracellular lipid signals, resulting in gene expression [19]. Thus, similar to the case for macrophages, microenvironmental stimuli define a broad range of DC subsets that differ in terms of function, location, migratory properties, maturity, and activation status [20].