Mycoplasma membrane lipoproteins induced proinflammatory cytokines by a mechanism distinct from that of lipopolysaccharide.

To gain a clear understanding of the mechanisms by which mycoplasmas induced the expression of proinflammatory cytokines in monocytic cells, we have studied the induction of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, and IL-6 by mycoplasmas in three distinct human myelomonocytic cell lines in comparison with induction by lipopolysaccharide (LPS). HL-60 cell line did not release cytokines when induced with either LPS or mycoplasmas. In contrast to LPS, mycoplasmas failed to increase the weak levels of tumor necrosis factor alpha secreted by phorbol myristate acetate-differentiated U937 cells. In addition, Northern (RNA) blot analysis of cytokine expression in these cells showed that the induction of IL-1 beta by mycoplasmas involves, unlike that by LPS, posttranscriptional events. Interestingly, in THP-1 cells, cytokine induction pathways triggered by mycoplasmas remained operational under conditions where LPS pathways were abolished, suggesting functional independence. The study of cytokine-inducing activity displayed by distinct fractions derived from a series of different mycoplasma species demonstrated that lipid membrane constituents were largely responsible for these effects. Finally, we have demonstrated that tyrosine phosphorylation is a crucial event in the mycoplasma-mediated induction of proinflammatory cytokines in either THP-1 cells or human monocytes.