1. Ccl22/MDC, is a prostaglandin dependent pyrogen, acting in the anterior hypothalamus to induce hyperthermia via activation of brown adipose tissue.
- Author
-
Osborn O, Sanchez-Alavez M, Dubins JS, Gonzalez AS, Morrison B, Hadcock JR, and Bartfai T
- Subjects
- Adipose Tissue, Brown drug effects, Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Body Temperature drug effects, Chemokine CCL22 metabolism, Chemokine CCL22 pharmacology, Dinoprostone metabolism, Female, Fever chemically induced, Fever prevention & control, Gene Expression, Hypothalamus, Anterior drug effects, Indomethacin pharmacology, Male, Mice, Mice, Inbred C57BL, Positron-Emission Tomography, Preoptic Area drug effects, Preoptic Area metabolism, Pyrogens metabolism, Pyrogens pharmacology, Rats, Rats, Sprague-Dawley, Receptors, CCR4 genetics, Receptors, CCR4 metabolism, Reverse Transcriptase Polymerase Chain Reaction, Telemetry, Tomography, X-Ray Computed, Adipose Tissue, Brown metabolism, Chemokine CCL22 genetics, Fever physiopathology, Hypothalamus, Anterior metabolism
- Abstract
CC Chemokine ligand 22 (Ccl22) is a selective, high affinity ligand at the CC chemokine receptor 4 (Ccr4). We have identified cDNAs encoding both ligand and receptor of the Ccl22-Ccr4 pair in cDNA libraries of the anterior hypothalamus/pre-optic area (AH/POA) by PCR. The AH/POA is the key brain region where endogenous pyrogens have been shown to act on warm sensitive neurons to affect thermogenesis in brown adipose tissue (BAT) and other thermogenically responsive tissues. We show that functional Ccr4 receptors are present in the AH/POA neurons as injection of Ccl22 into the POA but not to other hypothalamic nuclei induces an increase in core body temperature as measured by radiotelemetry. Indomethacin (5 mg/kg s.c) pre-treatment markedly reduced the hyperthermia evoked by POA injection of Ccl22 (10 ng/0.5 ul) and thus suggests that this hyperthermia is mediated through cyclooxygenase activation and thus likely through the formation and action of the pyrogen prostaglandin E2. The temperature elevation involves a decrease in the respiratory exchange ratio and increased activation of the brown adipose tissue as demonstrated by ¹⁸F-FDG-PET imaging. We describe a novel role to the ligand Ccl22 and its receptor Ccr4 in the anterior hypothalamus in temperature regulation that depends on the synthesis of the endogenous pyrogen, prostaglandin E2., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF