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The interleukin-33 receptor contributes to pulmonary responses to ozone in male mice: role of the microbiome.
Respir Res 2019; 20(1):197RR

Abstract

BACKGROUND

Interleukin-33 is released in the airways following acute ozone exposure and has the ability to cause airway hyperresponsiveness, a defining feature of asthma. Ozone causes greater airway hyperresponsiveness in male than female mice. Moreover, sex differences in the gut microbiome account for sex differences in this response to ozone. The purpose of this study was to determine whether there were sex differences in the role of interleukin-33 in ozone-induced airway hyperresponsiveness and to examine the role of the microbiome in these events.

METHODS

Wildtype mice and mice genetically deficient in ST2, the interleukin-33 receptor, were housed from weaning with either other mice of the same genotype and sex, or with mice of the same sex but opposite genotype. At 15 weeks of age, fecal pellets were harvested for 16S rRNA sequencing and the mice were then exposed to air or ozone. Airway responsiveness was measured and a bronchoalveolar lavage was performed 24 h after exposure.

RESULTS

In same-housed mice, ozone-induced airway hyperresponsiveness was greater in male than female wildtype mice. ST2 deficiency reduced ozone-induced airway hyperresponsiveness in male but not female mice and abolished sex differences in the response to ozone. However, sex differences in the role of interleukin-33 were unrelated to type 2 cytokine release: ozone-induced increases in bronchoalveolar lavage interleukin-5 were greater in females than males and ST2 deficiency virtually abolished interleukin-5 in both sexes. Since gut microbiota contribute to sex differences in ozone-induced airway hyperresponsiveness, we examined the role of the microbiome in these ST2-dependent sex differences. To do so, we cohoused wildtype and ST2 deficient mice, a situation that allows for transfer of microbiota among cage-mates. Cohousing altered the gut microbial community structure, as indicated by 16S rRNA gene sequencing of fecal DNA and reversed the effect of ST2 deficiency on pulmonary responses to ozone in male mice.

CONCLUSIONS

The data indicate that the interleukin-33 /ST2 pathway contributes to ozone-induced airway hyperresponsiveness in male mice and suggest that the role of interleukin-33 is mediated at the level of the gut microbiome.

Authors+Show Affiliations

Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Av Bld1 room 319, Boston, MA, 02115, USA.Department of Biostatistics, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA.Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Av Bld1 room 319, Boston, MA, 02115, USA.Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Av Bld1 room 319, Boston, MA, 02115, USA.Department of Biostatistics, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA.Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Av Bld1 room 319, Boston, MA, 02115, USA. sshore@hsph.harvard.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31455422

Citation

Kasahara, David I., et al. "The Interleukin-33 Receptor Contributes to Pulmonary Responses to Ozone in Male Mice: Role of the Microbiome." Respiratory Research, vol. 20, no. 1, 2019, p. 197.
Kasahara DI, Wilkinson JE, Cho Y, et al. The interleukin-33 receptor contributes to pulmonary responses to ozone in male mice: role of the microbiome. Respir Res. 2019;20(1):197.
Kasahara, D. I., Wilkinson, J. E., Cho, Y., Cardoso, A. P., Huttenhower, C., & Shore, S. A. (2019). The interleukin-33 receptor contributes to pulmonary responses to ozone in male mice: role of the microbiome. Respiratory Research, 20(1), p. 197. doi:10.1186/s12931-019-1168-x.
Kasahara DI, et al. The Interleukin-33 Receptor Contributes to Pulmonary Responses to Ozone in Male Mice: Role of the Microbiome. Respir Res. 2019 Aug 27;20(1):197. PubMed PMID: 31455422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The interleukin-33 receptor contributes to pulmonary responses to ozone in male mice: role of the microbiome. AU - Kasahara,David I, AU - Wilkinson,Jeremy E, AU - Cho,Youngji, AU - Cardoso,Aline P, AU - Huttenhower,Curtis, AU - Shore,Stephanie A, Y1 - 2019/08/27/ PY - 2019/04/22/received PY - 2019/08/19/accepted PY - 2019/8/29/entrez PY - 2019/8/29/pubmed PY - 2019/8/29/medline KW - Airway responsiveness KW - IL-33 KW - Interleukin-5 KW - Neutrophil KW - Sex differences SP - 197 EP - 197 JF - Respiratory research JO - Respir. Res. VL - 20 IS - 1 N2 - BACKGROUND: Interleukin-33 is released in the airways following acute ozone exposure and has the ability to cause airway hyperresponsiveness, a defining feature of asthma. Ozone causes greater airway hyperresponsiveness in male than female mice. Moreover, sex differences in the gut microbiome account for sex differences in this response to ozone. The purpose of this study was to determine whether there were sex differences in the role of interleukin-33 in ozone-induced airway hyperresponsiveness and to examine the role of the microbiome in these events. METHODS: Wildtype mice and mice genetically deficient in ST2, the interleukin-33 receptor, were housed from weaning with either other mice of the same genotype and sex, or with mice of the same sex but opposite genotype. At 15 weeks of age, fecal pellets were harvested for 16S rRNA sequencing and the mice were then exposed to air or ozone. Airway responsiveness was measured and a bronchoalveolar lavage was performed 24 h after exposure. RESULTS: In same-housed mice, ozone-induced airway hyperresponsiveness was greater in male than female wildtype mice. ST2 deficiency reduced ozone-induced airway hyperresponsiveness in male but not female mice and abolished sex differences in the response to ozone. However, sex differences in the role of interleukin-33 were unrelated to type 2 cytokine release: ozone-induced increases in bronchoalveolar lavage interleukin-5 were greater in females than males and ST2 deficiency virtually abolished interleukin-5 in both sexes. Since gut microbiota contribute to sex differences in ozone-induced airway hyperresponsiveness, we examined the role of the microbiome in these ST2-dependent sex differences. To do so, we cohoused wildtype and ST2 deficient mice, a situation that allows for transfer of microbiota among cage-mates. Cohousing altered the gut microbial community structure, as indicated by 16S rRNA gene sequencing of fecal DNA and reversed the effect of ST2 deficiency on pulmonary responses to ozone in male mice. CONCLUSIONS: The data indicate that the interleukin-33 /ST2 pathway contributes to ozone-induced airway hyperresponsiveness in male mice and suggest that the role of interleukin-33 is mediated at the level of the gut microbiome. SN - 1465-993X UR - https://www.unboundmedicine.com/medline/citation/31455422/The_interleukin_33_receptor_contributes_to_pulmonary_responses_to_ozone_in_male_mice:_role_of_the_microbiome_ L2 - https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1168-x DB - PRIME DP - Unbound Medicine ER -