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Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Peron JP, de Brito AA, Pelatti M, Brandão WN, Vitoretti LB, Greiffo FR, da Silveira EC, Oliveira-Junior MC, Maluf M, Evangelista L, Halpern S, Nisenbaum MG, Perin P, Czeresnia CE, Câmara NO, Aimbire F, Vieira Rde P, Zatz M, de Oliveira AP - PLoS ONE (2015)

Bottom Line: Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease.We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage.These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10.

View Article: PubMed Central - PubMed

Affiliation: Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.

ABSTRACT
Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

No MeSH data available.


Related in: MedlinePlus

Reduced cytokine secretion in the lungs of htMSC and/or LLLT treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and BAL obtained for cytokine detection by the ELISA method for A)TNF-α, B)IL-6 C)IL-1β D)IFN-γ E) IL-10 and F)KC. Data representative of three independent experiments. n = 5–8 animals per group. One-way ANOVA.
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pone.0136942.g003: Reduced cytokine secretion in the lungs of htMSC and/or LLLT treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and BAL obtained for cytokine detection by the ELISA method for A)TNF-α, B)IL-6 C)IL-1β D)IFN-γ E) IL-10 and F)KC. Data representative of three independent experiments. n = 5–8 animals per group. One-way ANOVA.

Mentions: We next analyzed the amount of cytokines as IL-1β, IL-6, TNF-α, IFN-γ and the chemockine KC, to evaluate whether reduced cellularity in the lungs of our experimental culminated also in reduction of inflammatory mediators. Our results show that IL-1β was reduced when htMSCs either ip. or i.n. were associated with LLLT, although htMSCs i.n alone also reached significance (Fig 3C). The same pattern was observed for TNF-α (Fig 3A). KC, an important chemokine for the recruitment of neurotrophils, was reduced in all groups irrespective of the treatment (Fig 3F). Interestingly, IL-6 was reduced only when htMSCs were associated with LLL (Fig 3B) whereas no difference was observed for IFN-γ (Fig 3D) Very interestingly, the anti-inflammatory cytokine IL-10 was up-regulated only with LLL irradiation alone (Fig 3E).


Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Peron JP, de Brito AA, Pelatti M, Brandão WN, Vitoretti LB, Greiffo FR, da Silveira EC, Oliveira-Junior MC, Maluf M, Evangelista L, Halpern S, Nisenbaum MG, Perin P, Czeresnia CE, Câmara NO, Aimbire F, Vieira Rde P, Zatz M, de Oliveira AP - PLoS ONE (2015)

Reduced cytokine secretion in the lungs of htMSC and/or LLLT treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and BAL obtained for cytokine detection by the ELISA method for A)TNF-α, B)IL-6 C)IL-1β D)IFN-γ E) IL-10 and F)KC. Data representative of three independent experiments. n = 5–8 animals per group. One-way ANOVA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554986&req=5

pone.0136942.g003: Reduced cytokine secretion in the lungs of htMSC and/or LLLT treated animals.COPD animals were submitted to therapeutic protocols as described in materials and methods. Further, all animals were euthanized and BAL obtained for cytokine detection by the ELISA method for A)TNF-α, B)IL-6 C)IL-1β D)IFN-γ E) IL-10 and F)KC. Data representative of three independent experiments. n = 5–8 animals per group. One-way ANOVA.
Mentions: We next analyzed the amount of cytokines as IL-1β, IL-6, TNF-α, IFN-γ and the chemockine KC, to evaluate whether reduced cellularity in the lungs of our experimental culminated also in reduction of inflammatory mediators. Our results show that IL-1β was reduced when htMSCs either ip. or i.n. were associated with LLLT, although htMSCs i.n alone also reached significance (Fig 3C). The same pattern was observed for TNF-α (Fig 3A). KC, an important chemokine for the recruitment of neurotrophils, was reduced in all groups irrespective of the treatment (Fig 3F). Interestingly, IL-6 was reduced only when htMSCs were associated with LLL (Fig 3B) whereas no difference was observed for IFN-γ (Fig 3D) Very interestingly, the anti-inflammatory cytokine IL-10 was up-regulated only with LLL irradiation alone (Fig 3E).

Bottom Line: Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease.We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage.These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10.

View Article: PubMed Central - PubMed

Affiliation: Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.

ABSTRACT
Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

No MeSH data available.


Related in: MedlinePlus