FIGURE 19.10.

Comparison of the regulation and production of interleukin-1 (IL1), IL6 and activin A in the monocyte/macrophage and Sertoli cell.

(A) Activation of the TLR4 complex on the surface of the macrophage by bacterial lipopolysaccharide (LPS) upregulates expression of both IL1α and IL1β, which subsequently are processed to their mature bioactive 17-kDa forms by the action of calpain and caspase-1, respectively. IL1α tends to remain associated with the cell, but IL1β is secreted upon cleavage and binds to the IL1 receptor (IL1R1) on the cell surface to stimulate production of other inflammatory cytokines, such as IL6 and activin A. (B) The Sertoli responds to stimulation by LPS, spermatocytes and the residual cytoplasm of released spermatozoa by producing IL1α, preferentially. Two alternate transcripts of IL1α are produced by the Sertoli cell, including a transcript lacking the calpain cleavage site domain, which encodes a 24-kDa form of IL1α with reduced bioactivity. Both forms appear to be secreted by the adult Sertoli cell and both are able to signal via the IL1 receptor to stimulate the production of IL6 and activin A.