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MAP KINASE SIGNALING IN PULMONARY FIBROBLASTS EXPOSED TO PARTICULATE MATTER (PM) AND BRONCHOAL VEOLAR LAVAGE FLUID (BALF) FROM HEALTHY AND HYPERTENSIVE RATS
Citation:
Zhang, P. AND U P. Kodavanti. MAP KINASE SIGNALING IN PULMONARY FIBROBLASTS EXPOSED TO PARTICULATE MATTER (PM) AND BRONCHOAL VEOLAR LAVAGE FLUID (BALF) FROM HEALTHY AND HYPERTENSIVE RATS. Presented at American Thoracic Society, Atlanta, GA, May 17-22, 2002.
Description:
MAP KINASE SIGNALING IN PULMONARY FIBROBLASTS EXPOSED TO PARTICULATE MATTER (PM) AND BRONCHOALVEOLAR LAVAGE FLUID (BALF) FROM HEALTHY AND HYPERTENSIVE RATS. 1P Zhang, UP Kodavanti. NHEERL, US EPA, Research Triangle Park, 1School of Vet Med, NCSU, Raleigh, NC
Exposure to PM may result in pulmonary inflammation and injury. We hypothesized that (A) both PM and inflammatory mediators in the BALF would stimulate pulmonary myofibroblast MAPK pathways which could modulate lung interstitial changes, and further that (B) BALF from cardiopulmonary compromised rats would elicit even greater response. MAPKs (ERK, JNK and p38 MAPK) have recently been recognized as major signaling proteins in many cell types. Activation of p38 MAPK or ERK requires phosphorylation of inactive protein, detectable by immunoblotting with phospho-specific antibodies. We compared the effect on activation of p38 MAPK and ERK in rat primary pulmonary myofibroblasts (from Sprague Dawley rats) following direct stimulation with PM, or with BALF derived from control, ambient-PM, or combustion PM-exposed normotensive Wistar Kyoto (WKY) and Spontaneously Hypertensive (SH) rats. Direct stimulation of fibroblasts with PM alone resulted in activation of p38 MAPK and ERK. While BALF from control WKY and SH rats had no effect on fibroblast ERK or p38 MAPK activation, BALF from PM-exposed WKY rats induced a little ERK and p38 MAPK phosphorylation, but BALF from PM-exposed SH rats was the most potent. Interestingly, PM-stimulated activation of p38 MAPK and ERK were more susceptible to inhibition by SB239063 and PD98059, respectively, than BALF-stimulated activation of these MAPKs. These results demonstrate the potential relationship between hypertension and MAPKs-mediated pulmonary inflammation in response to PM. Furthermore, our results indicate that inflammatory mediators in BALF may enhance the responsiveness of pulmonary fibroblasts which could delay remodeling of the lung in cardiovascular-compromised rats. (This abstract does not reflect the US EPA policy).
Cooperative agreement between USEPA and NCSU, #CT826512