| First Author | Leu SW | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 1 | Pages | 556-62 |
| PubMed ID | 21098223 | Mgi Jnum | J:168009 |
| Mgi Id | MGI:4881597 | Doi | 10.4049/jimmunol.1001630 |
| Citation | Leu SW, et al. (2011) TLR4 through IFN-beta promotes low molecular mass hyaluronan-induced neutrophil apoptosis. J Immunol 186(1):556-62 |
| abstractText | Intratracheal administration of low molecular mass (LMM) hyaluronan (200 kDa) results in greater neutrophil infiltration in the lungs of TLR4(-/-) mice compared with that in wild-type mice. In general, enhanced neutrophil infiltration in tissue is due to cell influx; however, neutrophil apoptosis also plays an important role. We have assessed the effects of TLR4 in the regulation of neutrophil apoptosis in response to administration of LMM hyaluronan. We found that apoptosis of inflammatory neutrophils is impaired in TLR4(-/-) mice, an effect that depends upon the IFN-beta-mediated TRAIL/TRAILR system. IFN-beta levels were decreased in LMM hyaluronan-treated TLR4-deficient neutrophils. The treatment of inflammatory neutrophils with IFN-beta enhanced the levels of TRAIL and TRAILR 2. LMM hyaluronan-induced inflammatory neutrophil apoptosis was substantially prevented by anti-TRAIL neutralizing mAb. We conclude that decreased IFN-beta levels decrease the activity of the TRAIL/TRAILR system in TLR4-deficient neutrophils, leading to impaired apoptosis of neutrophils and resulting in abnormal accumulation of neutrophils in the lungs of LMM hyaluronan-treated mice. Thus, TLR4 plays a novel homeostatic role in noninfectious lung inflammation by accelerating the elimination of inflammatory neutrophils. |
