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IL-33 Drives Augmented Responses to Ozone in Obese Mice.
Environ Health Perspect 2017; 125(2):246-253EH

Abstract

BACKGROUND

Ozone increases IL-33 in the lungs, and obesity augments the pulmonary effects of acute ozone exposure.

OBJECTIVES

We assessed the role of IL-33 in the augmented effects of ozone observed in obese mice.

METHODS

Lean wildtype and obese db/db mice were pretreated with antibodies blocking the IL-33 receptor, ST2, and then exposed to ozone (2 ppm for 3 hr). Airway responsiveness was assessed, bronchoalveolar lavage (BAL) was performed, and lung cells harvested for flow cytometry 24 hr later. Effects of ozone were also assessed in obese and lean mice deficient in γδ T cells and their wildtype controls.

RESULTS AND DISCUSSION

Ozone caused greater increases in BAL IL-33, neutrophils, and airway responsiveness in obese than lean mice. Anti-ST2 reduced ozone-induced airway hyperresponsiveness and inflammation in obese mice but had no effect in lean mice. Obesity also augmented ozone-induced increases in BAL CXCL1 and IL-6, and in BAL type 2 cytokines, whereas anti-ST2 treatment reduced these cytokines. In obese mice, ozone increased lung IL-13+ innate lymphoid cells type 2 (ILC2) and IL-13+ γδ T cells. Ozone increased ST2+ γδ T cells, indicating that these cells can be targets of IL-33, and γδ T cell deficiency reduced obesity-related increases in the response to ozone, including increases in type 2 cytokines.

CONCLUSIONS

Our data indicate that IL-33 contributes to augmented responses to ozone in obese mice. Obesity and ozone also interacted to promote type 2 cytokine production in γδ T cells and ILC2 in the lungs, which may contribute to the observed effects of IL-33. Citation: Mathews JA, Krishnamoorthy N, Kasahara DI, Cho Y, Wurmbrand AP, Ribeiro L, Smith D, Umetsu D, Levy BD, Shore SA. 2017. IL-33 drives augmented responses to ozone in obese mice. Environ Health Perspect 125:246-253; http://dx.doi.org/10.1289/EHP272.

Authors+Show Affiliations

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27472835

Citation

Mathews, Joel A., et al. "IL-33 Drives Augmented Responses to Ozone in Obese Mice." Environmental Health Perspectives, vol. 125, no. 2, 2017, pp. 246-253.
Mathews JA, Krishnamoorthy N, Kasahara DI, et al. IL-33 Drives Augmented Responses to Ozone in Obese Mice. Environ Health Perspect. 2017;125(2):246-253.
Mathews, J. A., Krishnamoorthy, N., Kasahara, D. I., Cho, Y., Wurmbrand, A. P., Ribeiro, L., ... Shore, S. A. (2017). IL-33 Drives Augmented Responses to Ozone in Obese Mice. Environmental Health Perspectives, 125(2), pp. 246-253. doi:10.1289/EHP272.
Mathews JA, et al. IL-33 Drives Augmented Responses to Ozone in Obese Mice. Environ Health Perspect. 2017;125(2):246-253. PubMed PMID: 27472835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-33 Drives Augmented Responses to Ozone in Obese Mice. AU - Mathews,Joel A, AU - Krishnamoorthy,Nandini, AU - Kasahara,David Itiro, AU - Cho,Youngji, AU - Wurmbrand,Allison Patricia, AU - Ribeiro,Luiza, AU - Smith,Dirk, AU - Umetsu,Dale, AU - Levy,Bruce D, AU - Shore,Stephanie Ann, Y1 - 2016/07/29/ PY - 2015/10/31/received PY - 2016/02/23/revised PY - 2016/06/07/accepted PY - 2016/7/30/pubmed PY - 2017/8/25/medline PY - 2016/7/30/entrez SP - 246 EP - 253 JF - Environmental health perspectives JO - Environ. Health Perspect. VL - 125 IS - 2 N2 - BACKGROUND: Ozone increases IL-33 in the lungs, and obesity augments the pulmonary effects of acute ozone exposure. OBJECTIVES: We assessed the role of IL-33 in the augmented effects of ozone observed in obese mice. METHODS: Lean wildtype and obese db/db mice were pretreated with antibodies blocking the IL-33 receptor, ST2, and then exposed to ozone (2 ppm for 3 hr). Airway responsiveness was assessed, bronchoalveolar lavage (BAL) was performed, and lung cells harvested for flow cytometry 24 hr later. Effects of ozone were also assessed in obese and lean mice deficient in γδ T cells and their wildtype controls. RESULTS AND DISCUSSION: Ozone caused greater increases in BAL IL-33, neutrophils, and airway responsiveness in obese than lean mice. Anti-ST2 reduced ozone-induced airway hyperresponsiveness and inflammation in obese mice but had no effect in lean mice. Obesity also augmented ozone-induced increases in BAL CXCL1 and IL-6, and in BAL type 2 cytokines, whereas anti-ST2 treatment reduced these cytokines. In obese mice, ozone increased lung IL-13+ innate lymphoid cells type 2 (ILC2) and IL-13+ γδ T cells. Ozone increased ST2+ γδ T cells, indicating that these cells can be targets of IL-33, and γδ T cell deficiency reduced obesity-related increases in the response to ozone, including increases in type 2 cytokines. CONCLUSIONS: Our data indicate that IL-33 contributes to augmented responses to ozone in obese mice. Obesity and ozone also interacted to promote type 2 cytokine production in γδ T cells and ILC2 in the lungs, which may contribute to the observed effects of IL-33. Citation: Mathews JA, Krishnamoorthy N, Kasahara DI, Cho Y, Wurmbrand AP, Ribeiro L, Smith D, Umetsu D, Levy BD, Shore SA. 2017. IL-33 drives augmented responses to ozone in obese mice. Environ Health Perspect 125:246-253; http://dx.doi.org/10.1289/EHP272. SN - 1552-9924 UR - https://www.unboundmedicine.com/medline/citation/27472835/IL_33_Drives_Augmented_Responses_to_Ozone_in_Obese_Mice_ L2 - https://ehp.niehs.nih.gov/doi/full/10.1289/EHP272?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -