Regulation of cysteine-rich intestinal protein, a zinc finger protein, by mediators of the immune response

Cysteine-rich intestinal protein (CRIP), a member of the LIM protein family , has a unique double zinc finger motif as the defining feature. GRIP is hi ghly expressed in intestine and immune cells. GRIP transgenic (Tg) mice and nontransgenic controls were challenged with lipopolysaccharide (LPS), Seru m concentrations of interferon-gamma and tumor necrosis factor-alpha were l ess while those of interleukin-6 and -10 were greater in the Tg mice follow ing LPS administration. CRIP-overexpressing splenocytes produce the same cy tokine profile. These responses are consistent with a regulatory role for t his protein in cell differentiation, which produces an imbalance in Th1 and Th2 cytokines. Stimulation of GRIP protein levels by LPS is eliminated in metallothionein knockout mice, suggesting metallothionein is the source of zinc for this zinc finger protein and, further, that this could reflect a r elationship to the zinc nutritional status and to the aberrant Th1/Th2 cyto kine balance observed in zinc deficiency.