MYCOPLASMA MEMBRANE LIPOPROTEINS INDUCE PROINFLAMMATORY CYTOKINES BY A MECHANISM DISTINCT FROM THAT OF LIPOPOLYSACCHARIDE

To gain a clear understanding of the mechanisms by which mycoplasmas i nduce 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 huma n myelomonocytic cell lines in comparison with induction by lipopolysa ccharide (LPS), HL-60 cell line did not release cytokines when induced with either LPS or mycoplasmas. In contrast to LPS, mycoplasmas faile d to increase the weak levels of tumor necrosis factor alpha secreted by phorbol myristate acetate-differentiated U937 cells, In addition, N orthern (RNA) blot analysis of cytokine expression in these cells show ed that the induction of IL-1 beta by mycoplasmas involves, unlike tha t by LPS, posttranscriptional events, Interestingly, in THP-1 cells, c ytokine induction pathways triggered by mycoplasmas remained operation al under conditions where LPS pathways were abolished, suggesting func tional independence, The study of cytokine-inducing activity displayed by distinct fractions derived from a series of different mycoplasma s pecies demonstrated that lipid membrane constituents were largely resp onsible for these effects, Finally, we have demonstrated that tyrosine phosphorylation is a crucial event in the mycoplasma-mediated inducti on of proinflammatory cytokines in either THP-1 cells or human monocyt es.