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44 AMBIENT PARTICULATE MATTER INDUCES MYOFIBROBLAST DIFFERENTIATION VIA MACROPHAGE-DEPENDENT TRANSFORMING GROWTH FACTOR b TYPE I (ALK5) SIGNALING.
  1. K. Thavarajah,
  2. R. Kalhan,
  3. A. Nair,
  4. M. C. Nlend,
  5. N. Wang,
  6. P. H.S. Sporn
  1. Northwestern University, Chicago, IL

Abstract

Rationale Increased levels of ambient particulate matter have been associated with increased pulmonary morbidity and mortality. To investigate if particulate matter induces airway remodeling, we studied the effects of particulate matter (< 10 μm in diameter) collected from Dusseldorf, Germany (DPM), on fibroblast to myofibroblast differentiation.

Methods Human fetal lung fibroblasts (IMR-90) were grown to subconfluence, serum-starved for 48 hours, and exposed to either TGF-b1 (2 ng/mL), DPM, or conditioned medium from human monocytic (THP-1) cells exposed to DPM. The role of TGF-b1 signaling was assessed by the addition of SB431542 (10 μM), a TGF-b type I (ALK5) receptor inhibitor. After 48 hours, cells were lysed and analyzed by immunoblot for a-smooth muscle actin (aSMA), a marker of myofibroblast differentiation.

Results Direct exposure of IMR-90 cells to DPM did not increase aSMA expression. However, conditioned medium of THP-1 cells exposed to DPM induced increased aSMA expression in fibroblasts. This increase was blocked by the ALK5 inhibitor SB431542.

Conclusions Ambient particulate matter triggers macrophage-dependent induction of myofibroblast differentiation via ALK5 receptor signaling. We speculate that particulate matter induces airway remodeling.

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