β2-Microglobulin, interleukin-31, and arachidonic acid metabolites (leukotriene B4 and thromboxane A2) are involved in chronic renal failure-associated itch-associated responses in mice.

Abstract

Chronic renal failure (CRF) is a progressive disease with severe pruritus and dry skin as the major symptoms. However, the mechanisms of CRF-induced pruritus remain unclear. In this study, 5/6 nephrectomized (NPCT) mice were used as a mouse model of CRF. Serum concentrations of blood urea nitrogen and creatinine in 5/6 NPCT mice were increased. The stratum corneum water content in the skin of 5/6 NPCT mice was decreased. These findings suggest that 5/6 nephrectomy in mice results in a phenotype resembling human CRF. 5/6 NPCT mice showed spontaneous scratching, which was inhibited by μ-opioid receptor antagonist, suggesting that the scratching is an itch-related response. The number of cutaneous mast cells was not altered in 5/6 NPCT mice compared with sham-operated mice. The H1 histamine-receptor antagonist, proteinase-activated receptor 2-neutralizing antibody, and 5-HT3-receptor antagonist did not inhibit spontaneous scratching in 5/6 NPCT mice; therefore, the role of mast cells and serotonin in spontaneous scratching appears to be minimal. The anti-allergy agent azelastine, BLT leukotriene (LT) B4 receptor antagonist, and TP thromboxane (TX) A2 receptor antagonist inhibited spontaneous scratching in 5/6 NPCT mice, suggesting that LTB4 and TXA2 are involved in CRF-induced pruritus. Interestingly, in the skin of 5/6 NPCT mice, levels of two newly identified pruritogens (β2-microglobulin and interleukin-31) were increased. Taken together, these findings suggest that 5/6 NPCT mice are useful for the study of itching in CRF. In addition to LTB4 and TXA2, it is also suggested that β2-microglobulin and interleukin-31 are involved in itching associated with CRF-induced pruritus.

• Authors: Sikai Li, Tsugunobu Andoh, Qun Zhang, Daisuke Uta, Yasushi Kuraishi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 847 Pg. 19-25 (Mar 15 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 30659825 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Globulins
• Interleukins
• Narcotic Antagonists
• interleukin-31, mouse
• Leukotriene B4
• Arachidonic Acid
• Thromboxane A2

Topics

• Animals
• Arachidonic Acid (metabolism)
• Disease Models, Animal
• Globulins (metabolism)
• Interleukins (metabolism)
• Kidney Failure, Chronic (metabolism)
• Leukotriene B4 (metabolism)
• Male
• Mast Cells (drug effects, metabolism)
• Mice
• Mice, Inbred ICR
• Narcotic Antagonists (pharmacology)
• Pruritus (metabolism)
• Thromboxane A2 (metabolism)