Capsaicin suppresses ciliary function, while inducing permeability in bronchial epithelial cell cultures of COPD patients

Halil Ibrahim Toy; Abdullah Burak Yildiz; Demet Tasdemir Kahraman; Sedat Ilhan; Oner Dikensoy; Hasan Bayram

doi:10.3389/fphar.2022.996046

Capsaicin suppresses ciliary function, while inducing permeability in bronchial epithelial cell cultures of COPD patients

Front Pharmacol. 2022 Oct 6:13:996046. doi: 10.3389/fphar.2022.996046. eCollection 2022.

Authors

Halil Ibrahim Toy^#^{1

2

3

4}, Abdullah Burak Yildiz^#⁵, Demet Tasdemir Kahraman^{1

6}, Sedat Ilhan^{1

7}, Oner Dikensoy⁸, Hasan Bayram^{1

8

9

10}

Affiliations

¹ Gaziantep University School of Medicine, Respiratory Research Laboratory, Gaziantep, Türkiye.
² Izmir Biomedicine and Genome Center, Izmir, Türkiye.
³ Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Türkiye.
⁴ Department of Epidemiology and Cancer Control, St. Jude Childrens Research Hospital, Memphis, TN, United States.
⁵ Koc University School of Medicine, Istanbul, Türkiye.
⁶ Gaziantep University, Faculty of Medicine, Department of Medical Biochemistry, Gaziantep, Türkiye.
⁷ Gaziantep University, Institute of Health Sciences, Department of Respiratory Biology, Gaziantep, Türkiye.
⁸ Department of Chest Diseases, Gaziantep University School of Medicine, Gaziantep, Türkiye.
⁹ Department of Pulmonary Medicine, Koc University School of Medicine, Istanbul, Türkiye.
¹⁰ Koc University Research Centre for Translational Medicine (KUTTAM), Koç University, Istanbul, Türkiye.

^# Contributed equally.

Abstract

Take Home Message: Capsaicin modified inflammatory response and caused toxicity in bronchial epithelial cultures from patients with COPD. More importantly, capsaicin decreased ciliary beat frequency and induced epithelial permeability and these effects were partially prevented by formoterol and roflumilast. Tear gas is widely used to halt mass demonstrations. Studies have reported its adverse effects on multiple organ systems; however, its effect on individuals with chronic respiratory diseases and the underlying mechanisms of these effects are unclear. For the first time in the literature, we investigated the effects of capsaicin, the active ingredient of tear gas, on bronchial epithelial cell (BEC) cultures obtained from well-characterized groups of nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). BEC cultures were incubated with 50-500 μM capsaicin in the absence and presence of formoterol (1μM) and roflumilast (0.1 μM) for 24 h. Ciliary beat frequency (CBF) and transepithelial electrical resistance (TEER) were assessed at T1/4, T1/2, T1, T2, T4, T6, and T24 h, whereas the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and lactate dehydrogenase (LDH) was measured at T24 h. Capsaicin (250 µM) significantly decreased CBF of all BEC cultures from T1/4 h to T24 h (p<0.05). Formoterol significantly prevented decreases in CBF induced by capsaicin. Higher concentrations of capsaicin (250-500 μM) significantly reduced TEER of BECs from nonsmokers (T2-T24 h), smokers (T24 h) and COPD patients (T2 and T24 h), which was partially prevented by roflumilast. Capsaicin (500 μM) decreased release of IL-8 (p<0.0001) and GM-CSF (p<0.05) while inducing release of LDH in BECs (p<0.05), and this was more prominent in BEC from patients with COPD. In conclusion, our findings demonstrate that capsaicin can suppress ciliary activity and cytokine release from BECs, induce BEC culture permeability and cellular toxicity and that these effects can be partially prevented by formoterol and roflumilast.

Keywords: airways; ciliary beat frequency (CBF); cytokine; formoterol; roflumilast; tear gas; transepithelial electrical resistance (TEER).