Increased circulatory levels of fractalkine (CX3CL1) are associated with inflammatory chemokines and cytokines in individuals with type-2 diabetes

Sardar Sindhu,Shamsha Ali,Ajit Wilson,Nadeem Akhter,Rasheed Ahmad,Asma Al-Hubail,Saad Al-Zanki,Areej Abu Al-Roub,Shaima Al-Beloushi,Hossein Arefanian

doi:10.1186/s40200-017-0297-3

Sardar Sindhu, Shamsha Ali + Show 8 more

Open Access

https://doi.org/10.1186/s40200-017-0297-3

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Abstract

BackgroundFractalkine (CX3CL1) is involved in the development of numerous inflammatory conditions including metabolic diseases. However, changes in the circulatory fractalkine levels in type-2 diabetes (T2D) and their relationship with inflammatory chemokines/cytokines remain unclear. The aim of the study was to determine the T2D-associated modulations in plasma fractalkine levels and investigate their relationship with circulatory chemokines/cytokines.MethodsA total of 47 plasma samples were collected from 23 T2D and 24 non-diabetic individuals selected over a wide range of body mass index (BMI). Clinical metabolic parameters were determined using standard commercial kits. Fractalkine and chemokines/cytokines were measured using Luminex X-MAP® technology. C-reactive protein (CRP) was measured by ELISA. The data were compared using unpaired t-test and the dependence between two variables was assessed by Pearson’s correlation coefficient (r).ResultsPlasma fractalkine levels were significantly higher (P = 0.005) in T2D patients (166 ± 14.22 pg/ml) as compared with non-diabetics (118 ± 8.90 pg/ml). In T2D patients, plasma fractalkine levels correlated positively (P ≤ 0.05) with inflammatory chemokines/cytokines including CCL3 (r = 0.52), CCL4 (r = 0.85), CCL11 (r = 0.51), CXCL1 (r = 0.67), G-CSF (r = 0.91), IFN-α2 (r = 0.97), IL-17A (r = 0.79), IL-1β (r = 0.97), IL-12P70 (r = 0.90), TNF-α (r = 0.58), and IL-6 (r = 0.60). In non-diabetic individuals, fractalkine levels correlated (P ≤ 0.05) with those of CCL4 (r = 0.49), IL-1β (r = 0.73), IL-12P70 (r = 0.41), and TNF-α (r = 0.50). Notably, plasma fractalkine levels in T2D patients associated with systemic inflammation (CRP) (r = 0.65, P = 0.02).ConclusionsThe altered plasma fractalkine levels associate differentially with inflammatory chemokines/cytokines in T2D patients which may have implications for T2D immunopathogenesis.

Highlights

Fractalkine (CX3CL1) is involved in the development of numerous inflammatory conditions including metabolic diseases
Fractalkine in diabetic individuals associates with most of inflammatory chemokines Since the inflammatory chemokines are regarded as key mediators for inflammatory immune cell recruitment and induction of chronic sub-acute inflammation, we further asked if the changes in fractalkine expression were related with systemic inflammatory chemokines in type-2 diabetes (T2D) and/or non-diabetic subjects
Our data show that the increased fractalkine levels in T2D patients (Fig. 2a–d) were positively correlated with systemic concentrations of CCL3 (r = 0.52, P = 0.013), CCL4 (r = 0.85, P < 0.0001), CCL11 (r = 0.51, P = 0.01), and CXCL1 (r = 0.67, P = 0.0005)

Summary

Introduction

Fractalkine (CX3CL1) is involved in the development of numerous inflammatory conditions including metabolic diseases. The elevated circulatory levels of CXCL1 and CXCL5 in T2D patients [9] and the increased CCL11 (Eotaxin) protein in serum and mRNA in visceral adipose tissue of obese mice and humans have been reported [10]; and these chemokines may affect the recruitment of eosinophils, basophils, neutrophils, and monocytes at the site(s) of inflammation These immune regulatory cells synthesize and release proinflammatory cytokines such as IL-1, IL-6, and TNF-α which are regarded as the key factors involved in metabolic dysregulation including glucose and lipid disorders and insulin resistance in T2D [11,12,13]. These changes correlated positively with signature inflammatory chemokines and cytokines in the circulation

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