Abstract: Poster Presentations |

Pneumocystis Carinii β-Glucan-induced Inflammatory Signaling in Alveolar Epithelial cells is Protein Kinase C-dependent FREE TO VIEW

Scott E. Evans, MD*; Peter Y. Hahn, MD; Theodore J. Kottom, MS; Andrew H. Limper, MD
Author and Funding Information

Mayo Clinic and Foundation, Rochester, MN


Chest. 2004;126(4_MeetingAbstracts):917S. doi:10.1378/chest.126.4_MeetingAbstracts.917S
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PURPOSE:  Robust inflammatory responses are observed in respiratory failure associated with Pneumocystis carinii (PC) pneumonia. Increasing evidence indicates that alveolar epithelial cells (AECs) not only promote PC attachment, but also contribute substantially to PC-induced inflammatory responses. Our laboratory has demonstrated that NκB is essential to PC β-glucan (PCBG)-induced inflammatory signaling. Herein, we assess the role of protein kinase C (PKC) in these responses.

METHODS:  For each experiment, primary rat AECs were isolated and cultured. AECs were exposed to PCBG in the presence or absence of PKC inhibitors, then the media was assayed for production of inflammatory cytokines. AEC nuclear translocation of NκB p50 subunit was assessed after PCBG stimulation, with or without PKC, MEK-1 and p38 inhibition. AEC PKC activation was also assayed by demonstration of PKC phosphorylation after PCBG challenge by Western blotting technique, with attention to the various PKC isoforms.

RESULTS:  While little was noted from unstimulated AECs, PCBG induced MIP-2 and TNF-α production from AECs. This response was blocked by both inhibition of NκB and PKC. PCBG-induced NκB activation was similarly blocked by PKC inhibition, though inhibition of MEK-1 and p38 had little effect. PCBG induced phosphorylation of PKC isoform theta, and to a lesser extent alpha.

CONCLUSION:  PCBG induces PKC activation in AECs, the inhibition of which significantly attenuates the expression of inflammatory mediators. PKC activation likely precedes NκB activation following PCBG challenge.

CLINICAL IMPLICATIONS:  Clinical outcomes in PC pneumonia are more closely linked to lung inflammation than organism burden. These data provide insight into novel therapeutic targets to manage exuberant host inflammatory responses.

DISCLOSURE:  S.E. Evans, None.

Wednesday, October 27, 2004

12:30 PM - 2:00 PM




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