Defect of calmodulin-binding protein in expression of interleukin-1β gene by LPS-nonresponder C3H HeJ mouse macrophages

Peritoneal macrophages of Lipopolysaccharide (LPS)-refractory C3H HeJ mouse failed to express the mRNA coding interleukin 1 (IL-1)β when stimulated by the Ca²⁺ ionophore A23187 or LPS, though macrophages of LPS-responsive C3H He responded to these stimulants. These results suggest that the defect of the response in C3H HeJ macrophages toward LPS stimulation may be related to the Ca²⁺-dependent signal pathway. The extracts from the C3H HeJ macrophages showed normal activities of both protein kinase C (PKC) and calmodulin (CaM) in comparison with those from LPS-responsive C3H He macrophages. However, one species of CaM-binding proteins could hardly be detected by the cross-linking assay with ¹²⁵I-CaM in C3H HeJ macrophages stimulated by LPS. These results suggest that the LPS-refractory site in C3H HeJ macrophages is related to the lack of this CaM-binding protein, and the Ca²⁺-dependent CaM system may play an important role in the activation of cells by LPS.