Premium
Resistin Gene Expression is Downregulated in CD 4 + T Helper Lymphocytes and CD 14 + Monocytes in Rheumatoid Arthritis Responding to TNF ‐ α Inhibition
Author(s) -
Nagaev I.,
Andersen M.,
Olesen M. K.,
Nagaeva O.,
Wikberg J.,
MinchevaNilsson L.,
Andersen G. N.
Publication year - 2016
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12464
Subject(s) - resistin , cd14 , cd8 , tumor necrosis factor alpha , immunology , immune system , cytokine , cd19 , medicine , adipokine , insulin resistance , insulin
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, pro‐fibrotic and possibly tolerogenic properties. The aim was to assess the reaction of RETN gene expression to TNF ‐ α 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 ‐ γ , TNF ‐ β , IL ‐1 β , TNF ‐ α , TGF ‐ β and IL ‐10 gene expressions in CD 14 + monocytes, CD 4 + T helper (Th) lymphocytes (ly), CD 8 + T cytotoxic (Tc) ly and CD 19 + B ly in active RA before and 3 months after start of TNF ‐ α I. Leucocyte subsets were separated by specific monoclonal antibody‐covered beads, RNA extracted and levels of RETN , Th1 response, inflammatory and regulatory cytokine mRNA s measured by quantitative reverse transcription‐polymerase chain reaction technique. We found that TNF ‐ α I caused a significant downregulation of RETN gene expression in CD 14 + monocytes and CD 4 + Th ly and was unchanged in CD 8 + Tc ly and CD 19 + B ly. Both in active RA and during TNF ‐ α I, RETN mRNA levels were significantly higher in CD 14 + monocytes than in all other examined cell types. In monocytes, fold change in RETN and TGF ‐ β gene expressions upon TNF ‐ α I correlated significantly. Our findings indicate that RETN has pro‐inflammatory as well as proresolving roles in active RA.