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Sex Hormones and Lung Inflammation

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Lung Inflammation in Health and Disease, Volume II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1304))

Abstract

Inflammation is a characteristic marker in numerous lung disorders. Several immune cells, such as macrophages, dendritic cells, eosinophils, as well as T and B lymphocytes, synthetize and release cytokines involved in the inflammatory process. Gender differences in the incidence and severity of inflammatory lung ailments including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), lung cancer (LC), and infectious related illnesses have been reported. Moreover, the effects of sex hormones on both androgens and estrogens, such as testosterone (TES) and 17β-estradiol (E2), driving characteristic inflammatory patterns in those lung inflammatory diseases have been investigated. In general, androgens seem to display anti-inflammatory actions, whereas estrogens produce pro-inflammatory effects. For instance, androgens regulate negatively inflammation in asthma by targeting type 2 innate lymphoid cells (ILC2s) and T-helper (Th)-2 cells to attenuate interleukin (IL)-17A-mediated responses and leukotriene (LT) biosynthesis pathway. Estrogens may promote neutrophilic inflammation in subjects with asthma and COPD. Moreover, the activation of estrogen receptors might induce tumorigenesis. In this chapter, we summarize the most recent advances in the functional roles and associated signaling pathways of inflammatory cellular responses in asthma, COPD, PF, LC, and newly occurring COVID-19 disease. We also meticulously deliberate the influence of sex steroids on the development and progress of these common and severe lung diseases.

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Abbreviations

AA:

Arachidonic acid

AC:

Adenylate cyclase

AECs:

Airway epithelial cells

AHR:

Airway hyperresponsiveness

AP-1:

Activator protein 1

AR:

Androgen receptor

ASM:

Airway smooth muscle

ASMCs:

Airway smooth muscle cells

BALF:

Bronchoalveolar lavage fluid

cAMP:

Cyclic adenosine monophosphate

CCL C-C:

chemokine ligand

CCR C-C:

chemokine receptor

CD:

Cluster of differentiation

cGMP:

Cyclic guanosine monophosphate

COPD:

Chronic obstructive pulmonary disease

CYP11A1:

P450 side chain cleavage enzyme

CYP17A1:

P450 17α-hydroxylase

DAMPs:

Danger-associated molecular patterns

DCs:

Dendritic cells

DHEA:

Dehydroepiandrosterone

E2:

17β-Estradiol

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EMT:

Epithelial-mesenchymal transition

eNOS:

Endothelial nitric oxide synthase

ERK:

Extracellular signal-regulated kinase

ERα:

Estrogen receptor alpha

ERβ:

Estrogen receptor beta

ET:

Endothelin

FEV1:

Forced expiratory volume in 1 second

FVC:

Forced vital capacity

G-CSF:

Granulocyte colony-stimulating factor

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HDM:

House dust mite

IFN-γ:

Interferon gamma

Ig:

Immunoglobulin

IL:

Interleukin

ILC2:

Type 2innate lymphoid cell

IPF:

Idiopathic pulmonary fibrosis

JNK:

Jun N-terminal kinase

LC:

Lung cancer

LTs:

Leukotrienes

MAPK:

Mitogen-activated protein kinase

MCP-1:

Monocyte chemoattractant protein-1

MMP:

Matrix metalloproteinase

NF-κB:

Nuclear factor kappa B

NO:

Nitric oxide

OC:

Oral contraceptives

OVA:

Ovalbumin

P4:

Progesterone

PAMPs:

Pathogen-associated molecular patterns

PBMCs:

Peripheral blood mononuclear cells

PEFR:

Peak expiratory flow rate

PF:

Pulmonary fibrosis

PI3K:

Phosphoinositide 3-kinase

PMA:

Perimenstrual asthma

PR:

Progesterone receptor

PRRs:

Pattern recognition receptors

ROS:

Reactive oxygen species

STAR:

Steroidogenic acute regulatory protein

TAM:

Tumor-associated macrophages

TES:

Testosterone

TGF-β1:

Transforming growth factor beta 1

Th:

T-helper cell

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor alpha

TSPO:

Translocator protein

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Acknowledgments

Jorge Reyes-García is grateful to Posgrado en Ciencias Biológicas UNAM and CONACYT for the support to obtain a postdoctoral fellowship (EPE 2019). Abril Carbajal-García is grateful to the Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, for the instruction received during her studies to get a Ph.D. degree. She received fellowship from the Consejo Nacional de Ciencia y Tecnología, México (application # 2018-000068-02NACF-17950; CVU 826027).

Declaration of Interest

Figures in this book chapter were created with BioRender.com. The authors declare that they do not have a conflict of interest or financial relationship that may have influenced the work.

Funding

This study was partly supported by grants from Dirección General de Asuntos del Personal Académico (DGAPA), Universidad Nacional Autónoma de México IN204319, and CONACYT 137725 to LM Montaño.

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  1. Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, Mexico City, Mexico

    Jorge Reyes-García, Luis M. Montaño & Abril Carbajal-García

  2. Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA

    Jorge Reyes-García & Yong-Xiao Wang

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    Yong-Xiao Wang

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Reyes-García, J., Montaño, L.M., Carbajal-García, A., Wang, YX. (2021). Sex Hormones and Lung Inflammation. In: Wang, YX. (eds) Lung Inflammation in Health and Disease, Volume II. Advances in Experimental Medicine and Biology, vol 1304. Springer, Cham. https://doi.org/10.1007/978-3-030-68748-9_15

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