Modulating asthma-COPD overlap responses with IL-17 inhibition

Leandro do Nascimento Camargo; Renato Fraga Righetti; Francine Maria de Almeida; Tabata Maruyama Dos Santos; Silvia Fukuzaki; Nilo Arthur Bezerra Martins; Miguel Cantadori Barbeiro; Beatriz Mangueira Saraiva-Romanholo; Fernanda Degobbi Tenorio Quirino Dos Santos Lopes; Edna Aparecida Leick; Carla Máximo Prado; Iolanda de Fátima Lopes Calvo Tibério

doi:10.3389/fimmu.2023.1271342

Modulating asthma-COPD overlap responses with IL-17 inhibition

Front Immunol. 2023 Oct 27:14:1271342. doi: 10.3389/fimmu.2023.1271342. eCollection 2023.

Authors

Leandro do Nascimento Camargo^{1

2}, Renato Fraga Righetti^{1

2}, Francine Maria de Almeida¹, Tabata Maruyama Dos Santos^{1

2}, Silvia Fukuzaki¹, Nilo Arthur Bezerra Martins¹, Miguel Cantadori Barbeiro¹, Beatriz Mangueira Saraiva-Romanholo¹, Fernanda Degobbi Tenorio Quirino Dos Santos Lopes¹, Edna Aparecida Leick¹, Carla Máximo Prado³, Iolanda de Fátima Lopes Calvo Tibério¹

Affiliations

¹ Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil.
² Serviço de Reabilitação, Hospital Sírio-Libanês, São Paulo, Brazil.
³ Department of Bioscience, Federal University of São Paulo, Santos, São Paulo, Brazil.

Abstract

Background: IL-17 is a modulator of the inflammatory response and is implicated in lung remodeling in both asthma and chronic obstructive pulmonary disease (COPD). Well as and probably in patients with asthma-COPD overlap (ACO).

Methods: In this study, we evaluated the response of the airways and alveolar septa to anti-IL-17 treatment in an ACO model. Fifty-six male BALB/c mice were sensitized with ovalbumin (OVA group), received porcine pancreatic elastase (PPE group), or both (ACO group). Mice were then treated with either anti-IL-17 monoclonal antibody or saline. We evaluated hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, and mean alveolar diameter. We quantified inflammatory, response, extracellular matrix remodeling, oxidative stress markers, and signaling pathway markers.

Results: Anti-IL-17 treatment in the ACO anti-IL-17 group reduced the maximum response of respiratory system Rrs, Ers, Raw, Gtis, this when compared to the ACO group (p<0.05). There was a reduction in the total number of inflammatory cells, neutrophils, and macrophages in the BALF in the ACO anti-IL-17 group compared to the ACO group (p<0.05). There was attenuated dendritic cells, CD4+, CD8+, FOXP3, IL-1β, IL-2, IL-6, IL-13, IL-17, IL-33 in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p<0.05). We observed a reduction of MMP-9, MMP-12, TIMP-1, TGF-β, collagen type I in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p < 0.05). We also observed a reduction of iNOS and 8-iso-PGF2α in the airways and in the alveolar septum was reduced in the ACO anti-IL-17group compared to the ACO group (p < 0.05). Regarding the signaling pathways, NF-kB, ROCK-1, and ROCK-2 in the airway and alveolar septum were attenuated in the ACO anti-IL-17 group when compared to the ACO group (p<0.05).

Conclusions: Our results suggest that inhibiting IL-17 modulates cell-associated cytokine production in lung tissue, extracellular matrix remodeling, and oxidative stress in ACO through the modulation of NF-kB and FOXP3.

Keywords: anti-IL-17; asthma; asthma-COPD overlap (ACO); extracellular matrix remodeling; inflammation; oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma*
Forkhead Transcription Factors
Interleukin-17
Male
Mice
NF-kappa B
Pulmonary Disease, Chronic Obstructive* / drug therapy
Swine

Substances

Forkhead Transcription Factors
Interleukin-17
NF-kappa B

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors express their gratitude to the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant 2018/02537-5, the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and the Laboratory of Medical Investigations (LIM-20 FMUSP) for their generous financial support.