Resistin Gene Expression is Downregulated in CD4(+) T Helper Lymphocytes and CD14(+) Monocytes in Rheumatoid Arthritis Responding to TNF-alpha Inhibition
2016 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 84, no 4, 229-236 p.Article in journal (Refereed) Published
Rheumatoid arthritis (RA) is caused by complex interactions between immune cells and sustained by Th1 response cytokines. Resistin [resistance to insulin; (RETN)] is an inflammatory cytokine, first discovered in murine adipocytes. In man, RETN is mainly secreted by monocytes. The distinct role of RETN in the immune reaction is uncertain; however, RETN has pro-inflammatory, profibrotic and possibly tolerogenic properties. The aim was to assess the reaction of RETN gene expression to TNF-alpha inhibition (I) in pathogenetic immune cell subsets in RA, in the context of Th1, inflammatory and regulatory cytokine gene expressions. Accordingly, we measured RETN, IFN-gamma, TNF-beta, IL-1 beta, TNF-alpha, TGF-beta and IL-10 gene expressions in CD14(+) monocytes, CD4(+) T helper (Th) lymphocytes (ly), CD8(+) T cytotoxic (Tc) ly and CD19(+) B ly in active RA before and 3 months after start of TNF-alpha I. Leucocyte subsets were separated by specific monoclonal antibody-covered beads, RNA extracted and levels of RETN, Th1 response, inflammatory and regulatory cytokine mRNAs measured by quantitative reverse transcription-polymerase chain reaction technique. We found that TNF-alpha I caused a significant downregulation of RETN gene expression in CD14(+) monocytes and CD4(+) Th ly and was unchanged in CD8(+) Tc ly and CD19(+) B ly. Both in active RA and during TNF-alpha I, RETN mRNA levels were significantly higher in CD14(+) monocytes than in all other examined cell types. In monocytes, fold change in RETN and TGF-beta gene expressions upon TNF-alpha I correlated significantly. Our findings indicate that RETN has pro-inflammatory as well as proresolving roles in active RA.
Place, publisher, year, edition, pages
2016. Vol. 84, no 4, 229-236 p.
Immunology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-308941DOI: 10.1111/sji.12464ISI: 000387048700005PubMedID: 27434862OAI: oai:DiVA.org:uu-308941DiVA: diva2:1051369
FunderSwedish Research Council, 2012-2761Swedish Cancer Society, AN 2013/439