Membrane-bound toll-like receptors are overexpressed in peripheral blood and synovial fluid mononuclear cells of enthesitis-related arthritis category of juvenile idiopathic arthritis (JIA–ERA) patients and lead to secretion of inflammatory mediators.
We examined expression and function of TLRs in enthesitis-related arthritis (ERA) patients. RNA levels of TLR1, TLR3, and TLRs 5–8 were measured in 24 ERA peripheral blood mononuclear cells (PBMC), 18 synovial fluid mononuclear cells (SFMC), and IRAK1, IRAK4, TRIF, TRAF3, and TRAF6 in 18 PBMC and 10 SFMC. IL-6 and IL-8 were measured in supernatants from ERA PBMC (n=7), SFMC (n=3), and healthy PBMC (n=5) cultured with ligands for TLR1/2 (Pam 3-cys), TLR3 (polyI:C), TLR5 (flagellin), and TLR2/6 (zymosan). TLRs 1, 3, 5, and 6 were measured in whole blood (n=20 ERA, seven healthy) and SFMC (n=2) by flow cytometry. ERA PBMC compared to healthy PBMC and SFMC compared to ERA PBMC had higher RNA expression of TLR1, TLR3, TLR5, TLR6, IRAK1, IRAK4, TRIF, TRAF3, and TRAF6. TLR7 and TLR8 RNA expression was similar in all study groups. IL-6 and IL-8 levels were higher in stimulated ERA SFMC compared to ERA PBMC and in ERA PBMC compared to control PBMC. TLRs 1, 3, and 6 were also overexpressed at the protein level.
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Arpita
A
Myles
Mujeeb T
MT
Rahman
Amita
A
Aggarwal
D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology; D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000276:immunology*; D002648:Child; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D012313:RNA / Q000235:genetics; D013582:Synovial Fluid / Q000166:cytology; D048008:TNF Receptor-Associated Factor 3 / Q000276:immunology; D048029:TNF Receptor-Associated Factor 6 / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
D033942:Adaptor Proteins, Vesicular Transport; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; C470409:TICAM1 protein, human; D048008:TNF Receptor-Associated Factor 3; D048029:TNF Receptor-Associated Factor 6; C090656:TRAF3 protein, human; D051193:Toll-Like Receptors; D012313:RNA; C507768:IRAK1 protein, human; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases