Leukotrienes and sex: strange bedfellows?

Smith, Lewis J.

doi:10.1172/jci95717

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…Eicosanoid formation is induced through stimuli on receptors strongly modulated by sex. The pro-inflammatory eicosanoids production is sex biased, indeed testosterone regulating the subcellular localization of the 5-lipoxygenase, a key enzime, drive the formation of leukotriene [28]. Several studies suggest that androgens suppress leukotriene levels, and female sex is associated with higher biosynthesis of these molecules.…”

Section: Hormones Chromosomes Immunity and Allergymentioning

confidence: 99%

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

Martinis

Sirufo

Suppa

et al. 2020

IJMS

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Allergies are rapidly worsening in recent decades, representing the most common immunological diseases. The mechanism of disorders such as asthma, rhinocongiuntivitis, urticaria, atopic dermatitis, food and drug allergies, and anaphylaxis still remain unclear and consequently treatments is mostly still symptomatic and aspecific while developments of new therapies are limited. A growing amount of data in the literature shows us how the prevalence of allergic diseases is different in both sexes and its changes over the course of life. Genes, hormones, environmental and immunological factors affect sex disparities associated with the development and control of allergic diseases, while they more rarely are considered and reported regarding their differences related to social, psychological, cultural, economic, and employment aspects. This review describes the available knowledge on the role of sex and gender in allergies in an attempt to improve the indispensable gender perspective whose potential is still underestimated while it represents a significant turning point in research and the clinic. It will offer insights to stimulate exploration of the many aspects still unknown in this relationship that could ameliorate the preventive, diagnostic, and therapeutic strategies in allergic diseases.

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Section: Hormones Chromosomes Immunity and Allergymentioning

confidence: 99%

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

Martinis

Sirufo

Suppa

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…The literature revealed that females are more likely to have 5-LO/5-LO-activating protein (FLAP) complex assembly at the nuclear membrane than males and that male hormones can inhibit the formation of this 5-LO/ FLAP complex. (53,54) Another fact is that females could be more susceptible to the development of inflammatory chronic disorders or autoimmune diseases than males. (55) Therefore, the underlying mechanism of these sex-specific effects should be further examined.…”

Section: Discussionmentioning

confidence: 99%

The Multifarious Functions of Leukotrienes in Bone Metabolism

Oliveira

Tokuhara

Veeriah

et al. 2023

J of Bone & Mineral Res

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Leukotrienes (LTs) are derived from arachidonic acid metabolism by the 5‐lipoxygenase (5‐LO) enzyme. The production of LTs is stimulated in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis, and periodontitis, with a relevant contribution to bone resorption. However, its role in bone turnover, particularly the suppression of bone formation by modulating the function of osteoclasts and osteoblasts, remains unclear. We investigated the effects of LTs on bone metabolism and their impact on osteogenic differentiation and osteoclastogenesis using a 5‐LO knockout (KO) mouse model. Results from micro‐computed tomography (μCT) analysis of femur from 8‐week‐old 5‐LO‐deficient mice showed increased cortical bone and medullary region in females and males and decreased trabecular bone in females. In the vertebra, we observed increased marrow area in both females and males 5‐LO KO and decreased trabecular bone only in females 5‐LO KO. Immunohistochemistry (IHC) analysis showed higher levels of osteogenic markers tissue‐nonspecific alkaline phosphatase (TNAP) and osteopontin (OPN) and lower expression of osteoclastogenic marker tartrate‐resistant acid phosphatase (TRAP) in the femurs of 5‐LO KO mice versus wild‐type (WT). Alkaline phosphatase activity and mineralization assay results showed that the 5‐LO absence enhances osteoblasts differentiation and mineralization but decreases the proliferation. Alkaline phosphatase (ALP), Bglap, and Sp7 gene expression were higher in 5‐LO KO osteoblasts compared to WT cells. Eicosanoids production was higher in 5‐LO KO osteoblasts except for thromboxane 2, which was lower in 5‐LO–deficient mice. Proteomic analysis identified the downregulation of proteins related to adenosine triphosphate (ATP) metabolism in 5‐LO KO osteoblasts, and the upregulation of transcription factors such as the adaptor‐related protein complex 1 (AP‐1 complex) in long bones from 5‐LO KO mice leading to an increased bone formation pattern in 5‐LO–deficient mice. We observed enormous differences in the morphology and function of osteoclasts with reduced bone resorption markers and impaired osteoclasts in 5‐LO KO compared to WT osteoclasts. Altogether, these results demonstrate that the absence of 5‐LO is related to the greater osteogenic profile. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Gender differences in Damp-Heat Syndrome: A review

Yuan

Wang

et al. 2021

Biomedicine & Pharmacotherapy

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Leukotrienes and sex: strange bedfellows?

Cited by 3 publications

References 18 publications

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

The Multifarious Functions of Leukotrienes in Bone Metabolism

Gender differences in Damp-Heat Syndrome: A review

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