Cytokine Modulation by the Porphyromonas gingivalis HtpG in THP-1 Cells

Periodontal diseases are infectious chronic inflammatory diseases whose pathogenesis is partly attributed to the innate immune response to the presence of microbial pathogen-associated molecular patterns (PAMPs). We have found elevated levels of antibodies reactive with Porphyromonas gingivalis HtpG, the bacterial homologue to the human heat shock protein 90 (Hsp90), associated with periodontal health. We propose that the P. gingivalis HtpG is a unique PAMP the recognition of which stimulates the host immune response to generate antibodies protective for periodontal disease, manifested by cytokine modulation in favor of a Th2 profile.

Objective: Our objective in this study was to evaluate the Porphyromonas gingivalis HtpG modulation of chemokines and cytokines in the THP-1 human monocytic cell line.

Methods: We used a recombinant P. gingivalis HtpG (Pg rHtpG) molecule to examine the contribution of the P. gingivalis HtpG to cytokine and chemokine modulation in human THP-1 monocytic cells using real-time PCR to evaluate cytokine and chemokine mRNA expression. We compared this expression profile to that of the P. gingivalis lipopolysaccharide (LPS).

Results: We obtained distinct cytokine mRNA expression profiles for each Pg rHtpG and P.gingivalis lipopolysaccharide (LPS). Stimulation by Pg rHtpG favored a predominantly Th2 cytokine profile elaborated by human THP-1 monocytic cells. The role of HtpG in leukocyte migration was supported by elevated levels of IL-8 and eotaxins.

Conclusions: Pg rHtpG and P. gingivalis LPS are unique PAMPs. We found the chemokine and cytokine mRNA expression profiles for Pg rHtpG and P.gingivalis LPS to be distinctly different. The significance of the difference in gene transcription patterns is not immediately obvious; contributing factors may include signaling via different receptors. We have shown that HtpG signals through CD91 and TLR4. Stimulation by Pg rHtpG favored a predominantly Th2 response by THP-1 cells, indicative of an adaptive immune response. Supported by NIH DE11117.