Rheumatology Advance Access originally published online on July 28, 2006
Rheumatology 2007 46(2):232-237; doi:10.1093/rheumatology/kel226
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Does HLA-B27 influence the monocyte inflammatory response to lipopolysaccharide?
Department of Medicine, School of Clinical Medicine, University of Cambridge, Addenbrookes Hospital and 1Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
Correspondence to: Dr Jane Goodall, University of Cambridge, School of Clinical Medicine, Box 157, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. E-mail: jcg23{at}medschl.cam.ac.uk
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Abstract |
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Objectives. How human leucocyte antigen B27 (HLA-B27) contributes towards arthritis susceptibility is still unclear, but effects on the response to bacteria unrelated to the classical antigen presenting role of B27 have been suggested. This study investigated whether HLA-B27 modulates the innate response to lipopolysaccharide (LPS), a component shared between all Gram negative bacteria that can trigger reactive arthritis.
Methods. Pools of U937 transfectants expressing either HLA-B27, HLA-A2 or the expression plasmid alone were differentiated with phorbol 12-myristate 13-acetate and stimulated with LPS. Supernatants were analysed for tumour necrosis factor-
(TNF-) secretion and the gene expression profiles of unstimulated and LPS-stimulated cells were determined by microarray analysis. Changes in gene expression that are indicative of an unfolded protein response (UPR) were also analysed by quantitative polymerase chain reaction (PCR).
Results. TNF- secretion, a biological marker of the inflammatory response to LPS, was not significantly different between U937-B27 and U937-control. No differences in gene expression between unstimulated U937-B27 and U937-control lines were detected. Both U937-control and U937-B27 exhibited a stereotypic response to LPS. Only one gene, OAS2, was differentially expressed by these cell lines, and this was confirmed by quantitative PCR. Analysis of XBP-1 splicing suggested that the UPR is induced following the LPS stimulation, but this increase was seen in all transfectants.
Conclusions. The expression of B27 does not profoundly alter the gene expression following LPS stimulation. Therefore, additional signals, such as those provided by cytokines or intracellular infection, may be required to reveal any influence of B27 expression on the inflammatory response.
KEY WORDS: HLA-B27, Ankylosing spondylitis, U937, LPS, Unfolded protein response, Inflammation, Microarray
Submitted 14 February 2006;
revised version accepted 23 May 2006.
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