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MUC18 regulates IL-13-mediated airway inflammatory response

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Abstract

Objective

To evaluate the effects of MUC18 on IL-13-mediated airway inflammatory responses in human airway epithelial cells and in mice.

Materials

Primary normal human tracheobronchial epithelial (HTBE) cells, wild-type (WT) and Muc18 knockout (KO) mice, and mouse tracheal epithelial cells (mTECs) were utilized.

Treatment

Cultured HTBE cells treated with MUC18 siRNA or MUC18 expressing lentivirus were incubated with IL-13 (10 ng/mL) for 24 h. Mice were intranasally instilled with 500 ng of IL-13 for 3 days. mTECs were treated with IL-13 (10 ng/mL) for 3 days.

Methods

PCR was used to measure mRNA expression. Western Blot and ELISAs were used to quantify protein expression. Cytospins of bronchoalveolar lavage (BAL) cells were used to obtain leukocyte differentials.

Results

MUC18 siRNA reduced IL-13-mediated eotaxin-3 (183 ± 44 vs. 380 ± 59 pg/mL, p < 0.05), while MUC18 overexpression increased IL-13-mediated eotaxin-3 (95 ± 3 vs. 58 ± 3 pg/mL, p < 0.05) in HTBE cells. IL-13-treated Muc18 KO mice had a lower percentage of neutrophils in BAL than WT mice (25 ± 3 vs. 35 ± 3%, p = 0.0565).

Conclusions

These results implicate MUC18 as a potential enhancer of airway inflammation in a type 2 cytokine (e.g., IL-13) milieu.

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Acknowledgements

This work was supported by Grants to Dr. Hong Wei Chu from the National Institutes of Health R01 HL122321 and R01 AI106287.

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Authors and Affiliations

  1. Department of Medicine, National Jewish Health, 1400 Jackson Street, Room A639, Denver, CO, 80206, USA

    Connor Stevenson, Di Jiang, Niccolette Schaefer, Yoko Ito, Reena Berman, Amelia Sanchez & Hong Wei Chu

Authors
  1. Connor Stevenson
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  2. Di Jiang
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  3. Niccolette Schaefer
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  4. Yoko Ito
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  5. Reena Berman
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  6. Amelia Sanchez
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  7. Hong Wei Chu
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Corresponding author

Correspondence to Hong Wei Chu.

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Responsible Editor: Bernhard Gibbs.

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Stevenson, C., Jiang, D., Schaefer, N. et al. MUC18 regulates IL-13-mediated airway inflammatory response. Inflamm. Res. 66, 691–700 (2017). https://doi.org/10.1007/s00011-017-1050-6

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  • DOI: https://doi.org/10.1007/s00011-017-1050-6

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