Mechanisms Driving Gender Differences in Asthma

Fuseini, Hubaida; Newcomb, Dawn C.

doi:10.1007/s11882-017-0686-1

Cited by 349 publications

(284 citation statements)

References 79 publications

Supporting

Mentioning

226

Contrasting

Unclassified

Order By: Relevance

“…For example, greater myogenic tone has been identified in the arteries of male rats over that in females (22,23). Furthermore, women have increased asthma prevalence with changes in pulmonary smooth muscle contractile behavior compared with men (24). Most notably, our group recently reported greater muscle contraction in male stomach muscle cells compared with the female counterparts (1).…”

Section: Discussionmentioning

confidence: 82%

Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

et al. 2018

View full text Add to dashboard Cite

Abstract. Evidence of sex-related differences in gastrointestinal (GI) functions has been reported in the literature. In addition, various GI disorders have disproportionate prevalence between the sexes. An essential step in the initiation of smooth muscle contraction is the phosphorylation of the 20-kDa regulatory myosin light chain (MLC 20 ) by the Ca 2+ /calmodulin-dependent myosin light chain kinase (MLCK). However, whether male stomach smooth muscle inherits different contractile signaling mechanisms for the regulation of MLC 20 phosphorylation from that in females has not been established. The present study was designed to investigate sex-associated differences in the regulation of MLC 20 phosphorylation and thus muscle contraction in gastric smooth muscle cells (GSMCs). Experiments were performed on GSMCs freshly isolated from male and female rats. Contraction of the GSMCs in response to acetylcholine (ACh), a muscarinic agonist, was measured via scanning micrometry in the presence or absence of the MLCK inhibitor, ML-7. Additionally, the protein levels of MLC 20 , MLCK and phosphorylated MLC 20 were measured by ELISA. The protein levels of MLC 20 and MLCK were indifferent between the sexes. ACh induced greater contraction (P<0.05) as well as greater MLC 20 phosphorylation (P<0.05) in male GSMCs compared with female. Pretreatment of GSMCs with ML-7 significantly reduced the ACh-induced contraction (P<0.05) and MLC 20 phosphorylation (P<0.05) in the male and female cells, and notably, abolished the contractile differences between the sexes. In conclusion, MLC 20 phosphorylation and thus muscle contraction may be activated to a greater extent in male rat stomach compared with that in females. IntroductionIt has been established in previous research that gastrointestinal (GI) motility function is affected by gender (1). Healthy women have also been identified to have slower gastric emptying of solids compared with men (2). This may explain why gastroparesis -a chronic stomach motility disorder in which there is a delayed gastric emptying of food without mechanical obstruction -is more common in women than men (3,4). Furthermore, previous studies assessing colonic motility have demonstrated faster colon transit (shorter transit time) in men compared with women (5-7). In one study, women exhibited less pressure activity in the colon, particularly in the transverse/descending colon, than men (8). Sex-associated differences were also evident in the anal sphincter contraction and anorectal motility (9). For instance, Sun and Read (10) identified that healthy men had stronger anal sphincter pressures compared with women. In the gallbladder, women have been observed to have a slower emptying rate than men under normal conditions, and this may explain the increased probability of gallstone development in women compared with men (11). Sex-dependent differences in esophageal motility in terms of duration and velocity of esophageal contraction have also been also reported (12).In addition, sex-associated differences h...

show abstract

Section: Discussionmentioning

confidence: 82%

Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Asthma prevalence increases in females at the time of puberty, and epidemiological studies have associated puberty, measured by increasing Tanner stages, with decreased asthma symptoms in boys and increased asthma symptoms in girls (Fu et al, 2014). Several studies in women showed changes in hormone levels, either during the menstrual cycle or in taking oral contraceptives, modulated asthma symptoms (Fuseini and Newcomb, 2017). However, the mechanisms by which sex hormones regulate asthma are not fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have shown that estrogen, signaling through estrogen receptor-β, increased MUC5AC expression and mucus production in cultured airway epithelial cells (Tam et al, 2014), suggesting that sex hormones may regulate mucus production through multiple pathways. Our studies did not determine the mechanisms by which ovarian hormones regulated ILC2-induced airway inflammation nor take into account other cell types, including T cells, macrophages, and dendritic cells that sex hormones are known to regulate (Fuseini and Newcomb, 2017). However, our results did show that ovarian hormones increased Alt Ext-induced IL-5+ ILC2, eosinophils in the BAL, and mucus production.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

et al. 2017

Self Cite

View full text Add to dashboard Cite

Summary Sex hormones regulate many autoimmune and inflammatory diseases, including asthma. As adults, asthma prevalence is 2-fold greater in women compared to men. Group 2 innate lymphoid cells (ILC2) are increased in asthma, and we investigated how testosterone attenuated ILC2 function. In patients with moderate to severe asthma, we determined that women had increased circulating ILC2 numbers compared to men. In mice, ILC2 from adult females had increased IL-2-mediated ILC2 proliferation versus ILC2 from adult males and pre-pubescent females and males. Further, 5α-dihydrotestosterone, a hormone downstream of testosterone, decreased lung ILC2 numbers and IL-5 and IL-13 expression from ILC2. In vivo, testosterone attenuated Alternaria extract-induced IL-5+ and IL-13+ ILC2 numbers and lung eosinophils by intrinsically decreasing lung ILC2 numbers and cytokine expression as well as decreasing expression of IL-33 and TSLP, ILC2 stimulating cytokines. Collectively, these findings provide a foundational understanding in the sexual dimorphism in ILC2 function.

show abstract

“…). Sex differences in lung disease incidence, prevalence, and severity have been noted for years, as well as increased prevalence rates for asthma, chronic obstructive pulmonary disease (COPD), and other inflammatory diseases in women versus men (Fuseini and Newcomb ; Tsiligianni et al. ; Center for Disease Control and Prevention, ; Shah and Newcomb ).…”

Section: Introductionmentioning

confidence: 99%

Modulation of the lung inflammatory response to ozone by the estrous cycle

et al. 2019

View full text Add to dashboard Cite

Emerging evidence suggests that sex differences exist in the control of lung innate immunity; however, the specific roles of sex hormones in the inflammatory response, and the mechanisms involved are unclear. Here, we investigated whether fluctuations in circulating hormone levels occurring in the mouse estrous cycle could affect the inflammatory response to air pollution exposure. For this, we exposed female mice (C57 BL /6J, 8 weeks old) at different phases of the estrous cycle to 2 ppm of ozone or filtered air ( FA ) for 3 h. Following exposure, we collected lung tissue and bronchoalveolar lavage fluid ( BAL ), and performed lung function measurements to evaluate inflammatory responses and respiratory mechanics. We found a differential inflammatory response to ozone in females exposed in the luteal phase (metestrus, diestrus) versus the follicular phase (proestrus, estrus). Females exposed to ozone in the follicular phase had significantly higher expression of inflammatory genes, including Ccl2, Cxcl2, Ccl20, and Il6, compared to females exposed in the luteal phase ( P < 0.05), and displayed differential activation of regulatory pathways. Exposure to ozone in the follicular phase also resulted in higher BAL neutrophilia, lipocalin levels, and airway resistance than exposure in the luteal phase ( P < 0.05). Together, these results show that the effects of ozone exposure in the female lung are affected by the estrous cycle phase, and potentially hormonal status. Future studies investigating air pollution effects and inflammation in women should consider the menstrual cycle phase and/or circulating hormone levels.

show abstract

Mechanisms Driving Gender Differences in Asthma

Cited by 349 publications

References 79 publications

Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

Gender differences in the regulation of MLC20 phosphorylation and smooth muscle contraction in rat stomach

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation

Modulation of the lung inflammatory response to ozone by the estrous cycle

Contact Info

Product

Resources

About