Far-infrared Irradiation Inhibits Proliferation of Human Upper Airway Epithelial Cells Via Protein Phosphatase 2A-promoted Dephosphorylation of P70 S6 Kinase

Overview

Journal Photochem Photobiol Sci

Publisher Springer

Specialties Biology
Chemistry

Date 2024 Oct 27

PMID 39461912

Authors

Nayoung Lee

Yun-Jin Hwang

Hyung Gyun Na

Du-Hyong Cho

Affiliations

Soon will be listed here.

Abstract

Far-infrared (FIR) ray, an invisible electromagnetic radiation with a wavelength of 3‒1000 μm, elicits various biological effects. Excessive proliferation of human upper airway epithelial cells (HUAEpCs) contributes to the development and exacerbation of nasal narrowing diseases, including nasal polyposis and chronic rhinosinusitis with nasal polyps (CRSwNP). Here, we investigated the molecular mechanisms through which FIR irradiation inhibits the proliferation of HUAEpCs. FIR irradiation significantly inhibited the proliferation of NCI-H292 cells without alteration in cell viability. The anti-proliferative effect of FIR radiation was accompanied by decreased phosphorylation of p70S6K at Thr (p-p70S6K-Thr), without changes in the phosphorylation of mammalian target of rapamycin and adenosine monophosphate-activated protein kinase (AMPK). Overexpression of p70S6K-T389E mutant gene, not dominant negative-AMPKα1 gene, significantly reversed FIR irradiation-inhibited p-p70S6K-Thr and cell proliferation. Cotreatment with okadaic acid or knockdown of protein phosphatase 2A catalytic subunit (PP2Ac) gene expression significantly reversed FIR irradiation-decreased p-p70S6K-Thr and cell proliferation. FIR irradiation remarkably promoted the physical association of p70S6K and PP2Ac without change in total PP2Ac expression. Hyperthermal stimulus (39 °C) did not alter p-p70S6K-Thr and cell proliferation. In line with NCI-H292 cell results, FIR irradiation, not hyperthermal stimulus, significantly decreased p-p70S6K-Thr and cell proliferation in primary human nasal turbinate and polyp epithelial cells. These results demonstrated that FIR irradiation decreased the proliferation of HUAEpCs through PP2A-mediated inhibition of p70S6K phosphorylation, independent of its hyperthermal effect. Our data suggest that FIR therapy can be used to treat upper airway narrowing epithelial hyperplastic diseases, including nasal polyposis and CRSwNP.

References

Vatansever F, Hamblin M . Far infrared radiation (FIR): its biological effects and medical applications. Photonics Lasers Med. 2013; 4:255-266. PMC: 3699878. DOI: 10.1515/plm-2012-0034. View

Hsu Y, Chen Y, Chen T, Sue Y, Cheng T, Chen J . Far-infrared therapy induces the nuclear translocation of PLZF which inhibits VEGF-induced proliferation in human umbilical vein endothelial cells. PLoS One. 2012; 7(1):e30674. PMC: 3264594. DOI: 10.1371/journal.pone.0030674. View

Beever R . Far-infrared saunas for treatment of cardiovascular risk factors: summary of published evidence. Can Fam Physician. 2009; 55(7):691-6. PMC: 2718593. View

Ishibashi J, Yamashita K, Ishikawa T, Hosokawa H, Sumida K, Nagayama M . The effects inhibiting the proliferation of cancer cells by far-infrared radiation (FIR) are controlled by the basal expression level of heat shock protein (HSP) 70A. Med Oncol. 2007; 25(2):229-37. PMC: 2386844. DOI: 10.1007/s12032-007-9020-4. View

Hattori T, Kokura S, Okuda T, Okayama T, Takagi T, Handa O . Antitumor effect of whole body hyperthermia with alpha-galactosylceramide in a subcutaneous tumor model of colon cancer. Int J Hyperthermia. 2007; 23(7):591-8. DOI: 10.1080/02656730701708328. View

Tam A, Wadsworth S, Dorscheid D, Paul Man S, Sin D . The airway epithelium: more than just a structural barrier. Ther Adv Respir Dis. 2011; 5(4):255-73. DOI: 10.1177/1753465810396539. View

Rogers D . Physiology of airway mucus secretion and pathophysiology of hypersecretion. Respir Care. 2007; 52(9):1134-46. View

Wang Y, Bai C, Li K, Adler K, Wang X . Role of airway epithelial cells in development of asthma and allergic rhinitis. Respir Med. 2008; 102(7):949-55. DOI: 10.1016/j.rmed.2008.01.017. View

Ha E, Rogers D . Novel Therapies to Inhibit Mucus Synthesis and Secretion in Airway Hypersecretory Diseases. Pharmacology. 2015; 97(1-2):84-100. DOI: 10.1159/000442794. View

10.

Maestrelli P, Saetta M, Mapp C, Fabbri L . Remodeling in response to infection and injury. Airway inflammation and hypersecretion of mucus in smoking subjects with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001; 164(10 Pt 2):S76-80. DOI: 10.1164/ajrccm.164.supplement_2.2106067. View

11.

KRAJINA Z, Zirdum A . Histochemical analysis of nasal polyps. Acta Otolaryngol. 1987; 103(5-6):435-40. View

12.

Norlander T, Fukami M, Westrin K, Stierna P, Carlsoo B . Formation of mucosal polyps in the nasal and maxillary sinus cavities by infection. Otolaryngol Head Neck Surg. 1993; 109(3 Pt 1):522-9. DOI: 10.1177/019459989310900322. View

13.

Haberal I, Corey J . The role of leukotrienes in nasal allergy. Otolaryngol Head Neck Surg. 2003; 129(3):274-9. DOI: 10.1016/S0194-5998(03)00601-6. View

14.

Skoner D . Complications of allergic rhinitis. J Allergy Clin Immunol. 2000; 105(6 Pt 2):S605-9. DOI: 10.1067/mai.2000.106150. View

15.

Magnuson B, Ekim B, Fingar D . Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem J. 2011; 441(1):1-21. DOI: 10.1042/BJ20110892. View

16.

Garcia D, Shaw R . AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance. Mol Cell. 2017; 66(6):789-800. PMC: 5553560. DOI: 10.1016/j.molcel.2017.05.032. View

17.

Jastrzebski K, Hannan K, Tchoubrieva E, Hannan R, Pearson R . Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function. Growth Factors. 2007; 25(4):209-26. DOI: 10.1080/08977190701779101. View

19.

Parrott L, Templeton D . Osmotic stress inhibits p70/85 S6 kinase through activation of a protein phosphatase. J Biol Chem. 1999; 274(35):24731-6. DOI: 10.1074/jbc.274.35.24731. View

20.

Peterson R, Desai B, Hardwick J, Schreiber S . Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein. Proc Natl Acad Sci U S A. 1999; 96(8):4438-42. PMC: 16350. DOI: 10.1073/pnas.96.8.4438. View

21.

Song S, Na H, Kwak S, Choi Y, Bae C, Kim Y . Changes in Mucin Production in Human Airway Epithelial Cells After Exposure to Electronic Cigarette Vapor With or Without Nicotine. Clin Exp Otorhinolaryngol. 2020; 14(3):303-311. PMC: 8373839. DOI: 10.21053/ceo.2020.01907. View