Anti-inflammatory properties of human serum IgA: induction of IL-1 receptor antagonist and Fc alpha R (CD89)-mediated down-regulation of tumour necrosis factor-alpha (TNF-alpha) and IL-6 in human monocytes.
A deregulated expression and/or release of large amounts of inflammatory cytokines such as IL-1 and TNF-alpha accounts for most pathophysiological events in a variety of systemic inflammatory diseases, the effect being mediated by the interaction of these cytokines with their respective receptors. IL-1 receptor antagonist (IL-1Ra), mainly produced by monocytes/macrophages, is an inhibitor of IL-1 activity. The present study shows that human serum IgA induces significant IL-1Ra release in human peripheral blood mononuclear cells and adherent monocytes. IgA induced higher levels of IL-1Ra than Haemophilus influenzae type b (Hib) expressing lipopolysaccharide (LPS), purified LPS or phorbol myristate acetate (PMA), without induction of IL-1 beta release, and even inhibited LPS-induced IL-1 beta release. Induction of IL-1Ra by IgA could be detected both at the mRNA and protein levels in resting and activated monocytes. Ligation of Fc alpha R with MoAb My-43 or treatment with human serum IgA induced protein tyrosine phosphorylation in human monocytes, and herbimycin A, a specific inhibitor of protein tyrosine kinase activity, inhibited IgA-induced IL-1Ra production, suggesting that Fc alpha R-mediated induction of tyrosine phosphorylation is required for the IgA-induced stimulation of IL-1Ra release. In addition, triggering of Fc alpha R with MoAb specifically down-regulated TNF-alpha and IL-6 release in human monocytes activated with Hib. By the induction of IL-1Ra and down-regulation of the release of inflammatory cytokines such as IL-1 beta, TNF-alpha and IL-6, interaction of IgA with human monocytes may actively contribute to the regulation of the inflammatory response.
Wolf
H M
HM
Institute of Immunology, University of Vienna, Austria.
Hauber
I
I
Gulle
H
H
Samstag
A
A
Fischer
M B
MB
Ahmad
R U
RU
Eibl
M M
MM
D000328:Adult; D015703:Antigens, CD / Q000187:drug effects* / Q000502:physiology*; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011961:Receptors, Fc / Q000187:drug effects* / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015703:Antigens, CD; C036832:Fc(alpha) receptor; C507763:IL1RN protein, human; D007070:Immunoglobulin A; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D011961:Receptors, Fc; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases