Inflammatory Arthritis

Introduction

Research is being carried out into the pathogenesis of inflammatory arthritis and its management, led by Dr Mohini Gray, and Dr Rob Van't Hof.

Dr Mohini Gray's research focuses on the mechanisms of joint inflammation with particular reference to investigating the role of apoptotic cells as regulators of macrophage function. When apoptotic cells are ingested by normal macrophages that have been activated by lipopolysaccharide, they stop producing pro-inflammatory cytokines like TNF and IL-1 and instead produce anti-inflammatory cytokines like TGF-beta and IL-10. Since the synovium in rheumatoid arthritis contains few apoptotic cells, it looks like macrophages within the inflamed joint are being denied the normal "suppressive" signals that apoptotic cells can elicit. Research by Dr Gray's group has shown that macrophages can be reprogrammed by a soluble factor (or factors) released by apoptotic cells. This raises the possibilty that identification of these factors, or the receptors they work through could represent a new way to supress inflammation and treat inflammatory arthritis (Gray et al. PNAS 2007;104:14080-14085)

Research that is being led by Dr Rob Van't Hof focuses on developing new drug treatments for arthritis. Previous research performed by Dr Van't Hof and other members of the unit resulted in the identification of a series of novel compounds that inhibit osteoclast activity and the resorption of bone (Van't Hof et al. J Bone Miner Res 2004;19:1651-1660) without inhibiting bone formation (Idris et al Endocrinology 2008;150:5-13)

Studies on the mechanism of action of these drugs revealed that they prevented activation of the NFkB pathway in osteoclasts and osteoclast precursors by RANKL. Further studies showed that they also prevented NFkB activation mediated by the inflammatory cytokine, tumour necrosis factor (TNF). Since overproduction of TNF is thought to play a key role in the pathogenesis of inflammatory conditions, including rheumatoid arthritis Dr Van't Hof is currently studying the effects of these molecules in various experimental models of arthritis.

	Introduction Contact	Inflammatory Arthritis Introduction Research is being carried out into the pathogenesis of inflammatory arthritis and its management, led by Dr Mohini Gray, and Dr Rob Van't Hof. Dr Mohini Gray's research focuses on the mechanisms of joint inflammation with particular reference to investigating the role of apoptotic cells as regulators of macrophage function. When apoptotic cells are ingested by normal macrophages that have been activated by lipopolysaccharide, they stop producing pro-inflammatory cytokines like TNF and IL-1 and instead produce anti-inflammatory cytokines like TGF-beta and IL-10. Since the synovium in rheumatoid arthritis contains few apoptotic cells, it looks like macrophages within the inflamed joint are being denied the normal "suppressive" signals that apoptotic cells can elicit. Research by Dr Gray's group has shown that macrophages can be reprogrammed by a soluble factor (or factors) released by apoptotic cells. This raises the possibilty that identification of these factors, or the receptors they work through could represent a new way to supress inflammation and treat inflammatory arthritis (Gray et al. PNAS 2007;104:14080-14085) Research that is being led by Dr Rob Van't Hof focuses on developing new drug treatments for arthritis. Previous research performed by Dr Van't Hof and other members of the unit resulted in the identification of a series of novel compounds that inhibit osteoclast activity and the resorption of bone (Van't Hof et al. J Bone Miner Res 2004;19:1651-1660) without inhibiting bone formation (Idris et al Endocrinology 2008;150:5-13) Studies on the mechanism of action of these drugs revealed that they prevented activation of the NFkB pathway in osteoclasts and osteoclast precursors by RANKL. Further studies showed that they also prevented NFkB activation mediated by the inflammatory cytokine, tumour necrosis factor (TNF). Since overproduction of TNF is thought to play a key role in the pathogenesis of inflammatory conditions, including rheumatoid arthritis Dr Van't Hof is currently studying the effects of these molecules in various experimental models of arthritis.
	Updated: Wed, 22nd September, 2010