Chlamydophila pneumoniae induces expression of Toll-like Receptor 4 and release of TNF-α and MIP-2 via an NF-κB pathway in rat type II pneumocytes

Abstract

The TLR4 protein expression in rat type II cells is likely to be mediated by a heat-sensitive C. pneumoniae protein that induces a fast Ca2+-mediated NF-kappaB activity, necessary for maintenance of TLR4 expression and TNF-alpha and MIP-2 release through possibly Rac and Rho protein-dependent mechanism. These results indicate that type II pneumocytes play an important role in the innate pulmonary immune system and in inflammatory response mechanism of the alveolus.

Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro

“…Cells were preincubated with or without PF5080 for 30 min at 37°C. Thereafter cells were incubated with C. pneumoniae, fixed in 1% paraformaldehyde/250 mM HEPES (pH 7.4) and permeabilized with 0.04% saponin as described (8). For staining of TNFR1 and TLR4 cells were incubated with rabbit IgG anti-TNFR1 (H-271) and goat IgG anti-TLR4 (L-14) (Santa Cruz Biotechnology) for 20 h at 4°C.…”

“…Staining was analyzed with a Zeiss laser scanning microscope LSM 510 META with Axiovert 200 M (Carl Zeiss Jena GmbH, Jena, Germany) as described (8). Images were taken using a Plan-Apochromat 63ϫ/1.4 oil immersion objective and fluorescence excitation at 488 nm (30 mW Ar laser), 543 nm (1 mW HeNe laser), and 405 nm (diode laser).…”

“…C. pneumoniae strain TW183 was cultured and purified as described (28). Isolation of rat ATII cells and incubation with C. pneumoniae were described in detail recently (8).…”

“…TLR signaling is partly mediated by the transcription factor NF-B, which controls the expression of many genes involved in the inflammatory response (9). C. pneumoniae-induced activation of NF-B leads to a release of the chemokine MIP-2 and the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-␣) (8) and its receptor tumor necrosis factor receptor 1 (TNFR1). Together, they play an important role in bacterial infections and modulate the inflammatory process (10).…”

“…Many of C. pneumoniae-induced effects are mediated by cytokines. C. pneumoniae act at the ATII cell membrane to induce the expression of TLR4 (8). TLR signaling is partly mediated by the transcription factor NF-B, which controls the expression of many genes involved in the inflammatory response (9).…”