Estrogen enhances expression of the complement C5a receptor and the C5a-agonist evoked calcium influx in hormone secreting neurons of the hypothalamus

Farkas, Imre; Varju, Patricia; Szabó, E; Hrabovszky, Erik; Okada, Noriko; Okada, Hidechika; Liposits, Zsolt

doi:10.1016/j.neuint.2007.09.014

Cited by 16 publications

(15 citation statements)

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“…In the present study, the positive correlation of hepatic C5L2 (and C5L2/C5aR ratio) with circulating estrogens (E1, E2) and the decrease in expression in postmenopausal women indirectly suggest an estrogenic influence. In vitro cellular and in vivo animal studies support the notion that estrogens increase adipose C3 expression [31] and neural C5aR expression [32] but have differential effects on C5L2 depending on estrogen receptor targeting (ER α and β ) in different tissues [33]. It is now well recognized that most tissues in both men and women are influenced by estrogens [40], and the liver is particularly sensitive, including effects on lipid metabolism [41].…”

Section: Discussionmentioning

confidence: 90%

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Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

et al. 2014

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Objective. Obesity is associated with metabolic dysfunction with sex differences and chronic, low-grade inflammation. We proposed that hepatic expression of immune complement C3 related receptors (C3aR, C5aR, and C5L2) would be associated with pre- or postmenopausal status and metabolic profile in severely obese women. We hypothesized that C5L2/C5aR ratio, potentially influencing the ASP/C5L2 metabolic versus C5a/C5aR immune response, would predict metabolic profiles after weight loss surgery. Materials and Methods. Fasting plasma (hormone, lipid, and enzyme analysis) and liver biopsies (RT-PCR gene expression) were obtained from 91 women during surgery. Results. Hepatic C5L2 mRNA expression was elevated in pre- versus postmenopausal women (P < 0.01) and correlated positively with circulating estradiol, estrone, ApoB, ApoA1, ApoA1/B, waist circumference, age, and LDL-C (all P < 0.05). While plasma ASP was lower in pre- versus postmenopausal women (P < 0.01), the hepatic C5L2/C5aR mRNA ratio was increased (P < 0.001) and correlated positively with estrone (P < 0.01) and estradiol (P < 0.001) and negatively with circulating ApoB and liver enzymes ALT, AST, and GGT (all P < 0.05). Over 12 months postoperatively, liver enzymes in low C5L2/C5aR mRNA ratio group remained higher (ALP and ALT, P < 0.05, AST and GGT, P < 0.001 2-way-ANOVA). Conclusion. C5L2-C5aR association with other mediators including estrogens may contribute to hepatic metabolic and inflammatory function.

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Section: Discussionmentioning

confidence: 90%

“…Recent studies have shown that 17 β -estradiol may play a role in reducing the inflammatory response in adipose tissue as well as the cardiovascular and neural systems [28–30]. Further, various cell studies have indicated that sex hormones may play a role in the regulation of C3 [31], C5aR [32, 33], and the C5L2/ASP response [34]. …”

Section: Introductionmentioning

confidence: 99%

Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

et al. 2014

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“…The presence of receptors for C5a and C3a has been detected in the central nervous system [7,8,33,40], and activation of these receptors in some central neurons results in increased [Ca 2+ ] i and inward membrane currents [8,33]. Likewise, in the present study, we could observe the presence of C5aR mRNA and elevated [Ca 2+ ] i responses by C5a and C3a in DRG neurons, supporting the possibility that activation or sensitization by C5a and C3a is produced by direct binding to their receptors on the peripheral terminal of nociceptors.…”

Section: Discussionmentioning

confidence: 99%

Nociceptive sensitization by complement C5a and C3a in mouse

Jang

Clark

et al. 2010

Pain

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Activation of the complement system by injury increases inflammation by producing complement fragments C5a and C3a which are able to recruit and activate immune cells. Complement activation may contribute to pain after inflammation and injury. In the present study, we examined whether C5a and C3a elicit nociception when injected into mouse hind paws in vivo, and whether C5a and C3a activate and/or sensitize mechanosensitive nociceptors when applied on peripheral terminals in vitro. We also examined the dorsal root ganglia (DRG) for C5a receptor (C5aR) mRNA and effects of C5a and C3a on intracellular Ca 2+ concentration ([Ca 2+ ] i ) using Ca 2+ imaging. Heat hyperalgesia was elicited by intraplantar injection of C5a, and mechanical hyperalgesia by C5a and C3a. After exposure to either C5a or C3a, C-nociceptors were sensitized to heat as evidenced by an increased proportion of heat responsive fibers, lowered response threshold to heat and increased action potentials during and after heat stimulation. A-nociceptors were activated by complement. However, no change was observed in mechanical responses of A-and C-nociceptors after C5a and C3a application. The presence of C5aR mRNA was detected in DRG. C5a and C3a application elevated [Ca 2+ ] i and facilitated capsaicin-induced [Ca 2+ ] i responses in DRG neurons. The results suggest a potential role for complement fragments C5a and C3a in nociception by activating and sensitizing cutaneous nociceptors.

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“…For example, 17-beta estradiol was found to increase IgG and IgM production in leukocytes that were activated by IL-10 in SLE patients (Folomeev et al 1992). Estrogens are also known to regulate the complement system in a variety of tissues (Rhen and Cidlowski 2006;Farkas et al 2008).…”

Section: Mammalian Immune System: a Comparison With Teleosts And Intementioning

confidence: 99%

The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review

2011

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During the last decade, a number of studies have shown that, in addition to their classically described reproductive function, estrogens and androgens also regulate the immune system in teleosts. Today, several molecules are known to interfere with the sex-steroid signaling. These chemicals are often referred to as endocrine disrupting contaminants (EDCs). We review the growing evidence that these compounds interfere with the fish immune system. These studies encompass a broad range of approaches from field studies to those at the molecular level. This integrative overview improves our understanding of the various endocrine-disrupting processes triggered by these chemicals. Furthermore, the research also explains why fish that have been exposed to EDCs are more sensitive to pathogens during gametogenesis. In this review, we first discuss the primary actions of sex-steroid-like endocrine disruptors in fish and the specificity of the fish immune system in comparison to mammals. Then, we review the known interactions between the immune system and EDCs and interpret the primary effects of sex steroids (estrogens and androgens) and their related endocrine disruptors on immune modulation. The recent literature suggests that immune parameters may be used as biomarkers of contamination by EDCs. However, caution should be used in the assessment of such immunotoxicity. In particular, more attention should be paid to the specificity of these biomarkers, the external/internal factors influencing the response, and the transduction pathways induced by these molecules in fish. The use of the well-known mammalian models provides a useful guide for future research in fish.

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Estrogen enhances expression of the complement C5a receptor and the C5a-agonist evoked calcium influx in hormone secreting neurons of the hypothalamus

Cited by 16 publications

References 50 publications

Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

Nociceptive sensitization by complement C5a and C3a in mouse

The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review

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