The role of some chemokines from the CXC subfamily in a mouse model of diabetic neuropathy.

Magdalena Zychowska,Dominika Pilat,Joanna Mika,Ewelina Rojewska

doi:10.1155/2015/750182

Abstract

The mechanism involved in the development of diabetic neuropathy is complex. Currently, it is thought that chemokines play an important role in this process. The aim of this study was to determine how the level of some chemokines from the CXC subfamily varies in diabetic neuropathy and how the chemokines affect nociceptive transmission. A single intraperitoneal (i.p.) injection of streptozotocin (STZ; 200 mg/kg) resulted in an increased plasma glucose. The development of allodynia and hyperalgesia was measured at day 7 after STZ administration. Using Antibody Array techniques, the increases in CXCL1 (KC), CXCL5 (LIX), CXCL9 (MIG), and CXCL12 (SDF-1) protein levels were detected in STZ-injected mice. No changes in CXCL11 (I-TAC) or CXCL13 (BLC) protein levels were observed. The single intrathecal (i.t.) administration of CXCL1, CXCL5, CXCL9, and CXCL12 (each in doses of 10, 100, and 500 ng/5 μL) shows their pronociceptive properties as measured 1, 4, and 24 hours after injection using the tail-flick, von Frey, and cold plate tests. These findings indicate that the chemokines CXCL1, CXCL5, CXCL9, and CXCL12 are important in nociceptive transmission and may play a role in the development of diabetic neuropathy.

Highlights

Diabetic neuropathy occurs in nearly 50% of patients with diabetes mellitus [1]
We have shown that, during streptozotocin-induced diabetic neuropathy, the level of some pronociceptive interleukins and proteins from the tumor necrosis factor family is upregulated [7], which suggests their role in diabetic neuropathic pain
Using quantitative real-time PCR (qRT-PCR) and the RayBio Antibody Array technique, we examined the mRNA and protein levels of CXCL1 (KC), CXCL5 (LIX), CXCL9 (MIG), CXCL11 (I-TAC), CXCL12 (SDF-1), and CXCL13 (BLC) in lumbar spinal cords of diabetic mice

Summary

Introduction

Diabetic neuropathy occurs in nearly 50% of patients with diabetes mellitus [1]. The mechanisms involved in the development of diabetic neuropathic pain are poorly understood due to their complexity. We have shown that, during streptozotocin-induced diabetic neuropathy, the level of some pronociceptive interleukins and proteins from the tumor necrosis factor family is upregulated [7], which suggests their role in diabetic neuropathic pain. Each of them exerts its biological effects through a G-protein coupled receptor [8] Their main function as chemoattractants is to guide the migration of receptor cells to the place of chemokine secretion. The activated microglia cells, resident macrophages of the central nervous system, play an important role in diabetic neuropathy [7, 14]. It seems that the chemokines may be crucial in the development and maintenance of diabetic neuropathic pain

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