Leptin is an eosinophil survival factor
ABSTRACT Leptin regulates food intake, as well as metabolic, endocrine, and immune functions. It exerts proliferative and antiapoptotic activities in a variety of cell types, including T cells. Leptin also stimulates macrophages and neutrophils, and its production is increased during inflammation.
We sought to examine the expression of leptin receptors on eosinophils and the effect of recombinant leptin on proapoptotic pathways in these cells.
The presence of leptin receptor was examined by means of RT-PCR and immunofluorescence analysis in freshly isolated blood eosinophils and tissue eosinophils. The effect of recombinant leptin on apoptotic pathways in eosinophils was studied by using flow cytometric, immunoblotting, and immunofluorescence techniques.
Human eosinophils express leptin surface receptors under in vitro and in vivo conditions, and leptin delays apoptosis of mature eosinophils in vitro. The antiapoptotic effects of leptin were concentration dependent and blocked by an anti-leptin receptor mAb. The efficacy of leptin to block eosinophil apoptosis was similar to that of GM-CSF. Leptin delayed the cleavage of Bax, as well as the mitochondrial release of cytochrome c and second mitochondria-derived activator of caspase, suggesting that it blocks proapoptotic pathways proximal to mitochondria in eosinophils. Using pharmacological inhibitors, we obtained evidence that leptin initiates a signaling cascade involving phosphatidylinositol-3-OH kinase and mitogen-activated protein kinase-dependent pathways in eosinophils.
Leptin is a survival cytokine for human eosinophils, a finding with potential pathologic relevance in allergic and parasitic diseases.
- SourceAvailable from: Vanessa Pinho
[Show abstract] [Hide abstract]
- "For instance some members of the Bcl-2 family are involved in eosinophil survival. Specifically , increased expression of Bcl-X L (Dibbert et al., 1998), maintained Bid cleavage (Segal et al., 2007), inhibition of Bax translocation to the mitochondria (Dewson et al., 2001), and delayed Bax cleavage (Conus et al., 2005) result in maintained mitochondrial integrity and inhibition of caspase activation (Dewson et al., 2001; Conus et al., 2005). Likewise, neutrophils express anti-apoptotic members (Bcl-X L , Bcl2A1 and Mcl-1) as well as pro-apoptotic proteins (Bax, Bak, Bid, Bim and Puma) and those proteins regulate constitutive as well as inducible apoptosis/survival pathways (Weinmann et al., 1999; Moulding et al., 2001; Guo et al., 2006; Cowburn et al., 2011). "
ABSTRACT: Inflammation is a beneficial host reaction to tissue damage and has the essential primary purpose of restoring tissue homeostasis. Inflammation plays a major role in containing and resolving infection and may also occur under sterile conditions. The cardinal signs of inflammation dolor, calor, tumor and rubor are intrinsically associated with events including vasodilatation, edema and leukocyte trafficking into the site of inflammation. If uncontrolled or unresolved, inflammation itself can lead to further tissue damage and give rise to chronic inflammatory diseases and autoimmunity with eventual loss of organ function. It is now evident that the resolution of inflammation is an active continuous process that occurs during an acute inflammatory episode. Successful resolution requires activation of endogenous programs with switch from production of pro-inflammatory towards pro-resolving molecules, such as specific lipid mediators and annexin A1, and the non-phlogistic elimination of granulocytes by apoptosis with subsequent removal by surrounding macrophages. These processes ensure rapid restoration of tissue homeostasis. Here, we review recent advances in the understanding of resolution of inflammation, highlighting the pharmacological strategies that may interfere with the molecular pathways which control leukocyte survival and clearance. Such strategies have proved beneficial in several pre-clinical models of inflammatory diseases, suggesting that pharmacological modulation of the resolution process may be useful for the treatment of chronic inflammatory diseases in humans.Pharmacology [?] Therapeutics 04/2013; 139(13). DOI:10.1016/j.pharmthera.2013.04.006 · 7.75 Impact Factor
Article: A Role of Leptin in Psoriasis?
- [Show abstract] [Hide abstract]
ABSTRACT: Asthma is a c hronic condition involving the respiratory sys tem. T he aim of t his w ork is to investigate serum leptin level in asthmatic children and to evaluate the relationship between concentration of serum l eptin and s ome parameters of atopy and a sthma. This cross section study was conducted at the outpatient p ulmonology c linic, d epartment o f p ediatric, C airo University. It included forty children with mild a nd mode rate persistent asthma, twenty two of them were boys and 20 healthy children as control group. We excl uded from the st udy children who receive st eroid treatment and who had peak exp iratory flow rate more than 90%. Detailed history was taken and f ull clinical examination was performed, pulmonary function t est was done by p eak expiratory flow rat e t est. Complete b lood picture and serum immunoglobulin E were done to all asthmatic children. In addition serum leptin concentration was assessed to all asthmatic and control gr oups. O ur re sults revealed that the mean serum leptin was sig nificantly higher in asthmatics than controls. The mean serum leptin ± s tandard dev iation in asthmatic p atients wa s 2.7 ± 0.86 ng/ml wh ile it wa s 1 .65 ± 0.5 ng/ml i n control gr oup (p=0.04). T he median of ser um leptin level was significantly higher in a sthmatic pat ients who di dn't receive exclusive br east feeding when compared to those who received exclusive breast feeding (p=0.001). Median serum leptin level was higher in patients with atopic than patients with non atopic asthma (p=0.0058). Patients with moderate asthma had higher leptin levels than those wi th mi ld as thma (p= 0.0001). Also concen tration of leptin w as higher in t he p resence of eosinophilia t han with norm al eosinophilic count (p=0.0014). As regard to the correlations between serum leptin l evel and some p arameters in ast hmatic c hildren, significant positive correlation w as id entified between leptin leve ls and body m ass index (r=0.582 and p=0.01). Also significant positive correlation was found between log of leptin a nd i mmunoglobulin E levels in t otal asthmatic p atients (r=0.509 and p= 0.015). Whereas significant negative correlation was detected bet ween log of leptin a nd peak expiratory flow r ate r esults (r = - 0.709). Our study showed that serum l eptin w as the most predictive factor o f asthma (p=0.03, odd ratio = 1.895 and 95% confidence index (CI) =1.009- 3.351) w hen compared to age, ge nder a nd body m ass in dex. S o we recommended more researches to identify t he role o f leptin in other i nflammatory and allergic d iseases.