PMID- 33730343 OWN - NLM STAT- MEDLINE DCOM- 20211223 LR - 20240215 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 44 IP - 4 DP - 2021 Aug TI - The MAPKinase Signaling and the Stimulatory Protein-1 (Sp1) Transcription Factor Are Involved in the Phototherapy Effect on Cytokines Secretion from Human Bronchial Epithelial Cells Stimulated with Cigarette Smoke Extract. PG - 1643-1661 LID - 10.1007/s10753-021-01448-5 [doi] AB - The present study was aimed to investigate the phototherapy effect with low-level laser on human bronchial epithelial cells activated by cigarette smoke extract (CSE). Phototherapy has been reported to actuate positively for controlling the generation/release of anti-inflammatory and pro-inflammatory mediators from different cellular type activated by distinct stimuli. It is not known whether the IL-8 and IL-10 release from CSE-stimulated human bronchial epithelium (BEAS) cells can be influenced by phototherapy. Human bronchial epithelial cell (BEAS) line was cultured in a medium with CSE and irradiated (660 nm) at 9 J. Apoptosis index was standardized with Annexin V and the cellular viability was evaluated by MTT. IL-8, IL-10, cAMP, and NF-kappaB were measured by ELISA as well as the Sp1, JNK, ERK1/2, and p38MAPK. Phototherapy effect was studied in the presence of mithramycin or the inhibitors of JNK or ERK. The IL-8, cAMP, NF-kappaB, JNK, p38, and ERK1/2 were downregulated by phototherapy. Both the JNK and the ERK inhibitors potentiated the phototherapy effect on IL-8 as well as on cAMP secretion from BEAS. On the contrary, IL-10 and Sp1 were upregulated by phototherapy. The mithramycin blocked the phototherapy effect on IL-10. The results suggest that phototherapy has a dual effect on BEAS cells because it downregulates the IL-8 secretion by interfering with CSE-mediated signaling pathways, and oppositely upregulates the IL-10 secretion through of Sp1 transcription factor. The manuscript provides evidence that the phototherapy can interfere with MAPK signaling via cAMP in order to attenuate the IL-8 secretion from CSE-stimulated BEAS. In addition, the present study showed that phototherapy effect is driven to downregulation of the both the IL-8 and the ROS secretion and at the same time the upregulation of IL-10 secretion. Besides it, the increase of Sp-1 transcription factor was crucial for laser effect in upregulating the IL-10 secretion. The dexamethasone corticoid produces a significant inhibitory effect on IL-8 as well as ROS secretion, but on the other hand, the corticoid blocked the IL-10 secretion. Taking it into consideration, it is reasonable to suggest that the beneficial effect of laser therapy on lung diseases involves its action on unbalance between pro-inflammatory and anti-inflammatory mediators secreted by human bronchial epithelial cells through different signaling pathway. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Brito, A AU - Brito A AD - Pos-graduation in Biophotonic, University Nove de Julho - Uninove, Sao Paulo, Sao Paulo, Brazil. FAU - Santos, T AU - Santos T AD - Pos-graduation in Biophotonic, University Nove de Julho - Uninove, Sao Paulo, Sao Paulo, Brazil. FAU - Herculano, K AU - Herculano K AD - Pos-graduation in Biophotonic, University Nove de Julho - Uninove, Sao Paulo, Sao Paulo, Brazil. FAU - Miranda, M AU - Miranda M AD - Pos-graduation in Biophotonic, University Nove de Julho - Uninove, Sao Paulo, Sao Paulo, Brazil. FAU - Sa, A K AU - Sa AK AD - Department of Science and Technology, Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, Rua Talim, no. 330 - Vila Nair, CEP: 12231-280, Sao Jose dos Campos, Sao Paulo, Brazil. FAU - Carvalho, J L AU - Carvalho JL AD - Department of Science and Technology, Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, Rua Talim, no. 330 - Vila Nair, CEP: 12231-280, Sao Jose dos Campos, Sao Paulo, Brazil. FAU - Albertini, R AU - Albertini R AD - Department of Science and Technology, Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, Rua Talim, no. 330 - Vila Nair, CEP: 12231-280, Sao Jose dos Campos, Sao Paulo, Brazil. FAU - Castro-Faria-Neto, H AU - Castro-Faria-Neto H AD - Laboratory of Immunopharmacology, Oswaldo Cruz Foundation - FioCruz, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Ligeiro-de-Oliveira, A P AU - Ligeiro-de-Oliveira AP AD - Pos-graduation in Biophotonic, University Nove de Julho - Uninove, Sao Paulo, Sao Paulo, Brazil. FAU - Aimbire, Flavio AU - Aimbire F AUID- ORCID: 0000-0002-4290-541X AD - Department of Science and Technology, Institute of Science and Technology, Federal University of Sao Paulo - UNIFESP, Rua Talim, no. 330 - Vila Nair, CEP: 12231-280, Sao Jose dos Campos, Sao Paulo, Brazil. flavio.aimbire@unifesp.br. LA - eng GR - 2012/16498-5/FAPESP/ PT - Journal Article DEP - 20210317 PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Cytokines) RN - 0 (Smoke) RN - 0 (Sp1 Transcription Factor) RN - 0 (SP1 protein, human) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) SB - IM MH - Bronchi/drug effects/metabolism MH - Cell Line MH - Cigarette Smoking/adverse effects/therapy MH - Cytokines/*metabolism MH - Humans MH - Mitogen-Activated Protein Kinase Kinases/*metabolism MH - Phototherapy/*methods MH - Respiratory Mucosa/drug effects/*metabolism MH - Smoke/*adverse effects MH - Sp1 Transcription Factor/*metabolism MH - Nicotiana/*adverse effects OTO - NOTNLM OT - COPD OT - IL-10 OT - bronchial epithelium OT - oxidative stress OT - photobiomodulation OT - transcription factors EDAT- 2021/03/18 06:00 MHDA- 2021/12/24 06:00 CRDT- 2021/03/17 17:50 PHST- 2018/06/20 00:00 [received] PHST- 2021/03/07 00:00 [accepted] PHST- 2019/11/01 00:00 [revised] PHST- 2021/03/18 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2021/03/17 17:50 [entrez] AID - 10.1007/s10753-021-01448-5 [pii] AID - 10.1007/s10753-021-01448-5 [doi] PST - ppublish SO - Inflammation. 2021 Aug;44(4):1643-1661. doi: 10.1007/s10753-021-01448-5. Epub 2021 Mar 17.