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Published on: July 26, 2017
TLR4 is a negative regulator in noninfectious lung inflammation
Hang Zhao1, Shaw-Wei Leu, Liyun Shi
1Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. hzhao5@partners.org
Journal of Immunology (Baltimore, Md. : 1950)
|April 2, 2010
Summary
Low molecular weight hyaluronan (LMW HA) induces lung inflammation in mice. Toll-like receptor 4 (TLR4) normally limits this inflammation, but its absence exacerbates the response, revealing a novel anti-inflammatory pathway.
Area of Science:
- Immunology
- Pulmonary Medicine
- Molecular Biology
Background:
- Low molecular weight hyaluronan (LMW HA) is known to induce pro-inflammatory responses in vitro.
- The in vivo effects of LMW HA on lung inflammation remain largely unexplored.
Purpose of the Study:
- To investigate the in vivo effects of LMW HA on mouse lung inflammation.
- To elucidate the role of Toll-like receptor 4 (TLR4) in LMW HA-induced lung inflammation.
Main Methods:
- Intratracheal administration of LMW HA (200 kDa) in mice.
- Assessment of inflammatory cell counts (neutrophils) and cytokine/chemokine levels.
- Evaluation of TLR4-deficient mice and MyD88-independent pathways.
Main Results:
- Intratracheal LMW HA administration induced significant lung inflammation.
- TLR4-deficient mice exhibited exacerbated inflammatory responses.
- TLR4-mediated signaling, independent of MyD88, involves IL-1 receptor antagonist production.
- Inhibition of pro-IL-1 beta promoted an anti-inflammatory response.
Conclusions:
- LMW HA is a potent inducer of lung inflammation in vivo.
- TLR4 plays a critical negative regulatory role in LMW HA-induced lung inflammation via a MyD88-independent pathway.
- Targeting TLR4-mediated IL-1R antagonist production may offer therapeutic strategies for LMW HA-induced lung inflammation.
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