“…For example, in addition to their association with disease severity in RA, 4 S100/calgranulins have been linked to disease progression in inflammatory bowel disease. 36,37 Furthermore, strongly increased expression of a member of this family of molecules, psoriasin, has been demonstrated in psoriatic lesions compared with adjacent unaffected skin in human subjects, 38 thus further supporting the premise that S100/calgranulins may not simply be 'innocent bystanders', but, rather, by virtue of their engagement of RAGE, 1 active participants in the host inflammatory response. We speculate that triggered by interaction with accumulating S100/calgranulins, activation of RAGE engages key signalling pathways linked to proinflammatory responses, such as MAP kinases and NF-B, thereby amplifying expression of molecules linked to chronic cellular perturbation and tissue destruction.…”