Type IVB Piliated Salmonella Typhi Induce IL-6 Production In Human Monocytic THP-1 Cells Through Activation Of PKC And ERK And NF-κB

Objective To investigate whether the production of interleukin-6 (IL-6) in THP-1 cells induced by the Type IVB piliated Salmonella Typhi through activation of PKC ERK and NF-kB, and whether the Type IVB pili can lead to pathological damage. Methods THP-1 cells were incubated with Typhi IVB piliated strain A21-6 or Typhi nonpiliated strain pits'; the amounts of IL-6 in cell culture supernatants were detected by ELISA method, and IL-6 mRNA expression was analyzed by RT-PCR. The activities of PKC, ERK and NF-kB were measured with substrate phosphorolysis kinase assay, Western Blot and luciferase reporter gene assay, respectively. The Type IVB piliated Salmonella Typhi strain A21-6 was used to stimulate the THP-1 cells or cells pretreated with PKC inhibitor DECA for different time interval, the activites of PKC and NF-kB was assayed at different time points; the production of IL-6 was quantitated at 5h point. Results The Type IVB piliated Salmonella Typhi strain A21-6 can stimulate significantly higher production of IL-6 and activities of PKC and ERK and NF-kB than those of Typhi nonpiliated strain pilS. After stimulation by the piliated bacteria in different time courses, the activities of PKC, ERK and NF-kB increased in a time-dependent fashion, and reached to the peak value at 30 min, 60 min and 120 min, respectively. The PKC inhibitor DECA remarkably reduced the production of IL-6, NF-kB and the activity of PKC induced by the piliated S. Typhi strain A21-6. Conclusion Our report demonstrated that the type IVB pili of S. Typhi played important roles in the production of the NF-kB and the proinflammatory cytokine IL-6, and in the stimulation of PKC and ERK activities and therefore, may have effects on the development of fever and other inflammatory responses. These results also suggest that PKC, ERK and NF-kB dependent pathway participates in the induction of IL-6 process.