Interleukin 1 receptor dependence of serum transferred arthritis can be circumvented by toll-like receptor 4 signaling.
Inflammatory arthritis is associated with the release of a network of key cytokines. In T cell receptor transgenic K/BxN mice interleukin (IL)-1 plays a key role in joint swelling and destruction, as suggested by the ability of anti-IL-1receptor (IL-1R) antibody treatment to delay the onset and slow the progression of this disease. This mechanism is dependent on the signaling pathway intermediary myeloid differentiation factor 88 (MyD88), such that neither IL-1R nor MyD88-deficient mice developed visually detectable synovitis after transfer of arthritogenic sera. The Toll-like receptors (TLRs) share the same signaling pathway through MyD88 as the IL-1R. The administration of a TLR-4 ligand, lipopolysaccharide, concomitant with arthritogenic serum in IL-1 receptor-deficient mice resulted in acute paw swelling, but not in MyD88-deficient mice. Also, serum transferred arthritis was not sustained in TLR-4 mutant mice compared with controls. These results suggest that innate immune functions via TLR-4 might perpetuate inflammatory mechanisms and bypass the need for IL-1 in chronic joint inflammation.
Choe
Jung-Yoon
JY
Division of Rheumatology, Allergy, and Immunology, and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA 92093, USA.
Crain
Brian
B
Wu
Sarah R
SR
Corr
Maripat
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000209:etiology*; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D007375:Interleukin-1 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D029721:Drosophila Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors