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Ccl22/MDC, is a prostaglandin dependent pyrogen, acting in the anterior hypothalamus to induce hyperthermia via activation of brown adipose tissue.
- Source :
-
Cytokine [Cytokine] 2011 Mar; Vol. 53 (3), pp. 311-9. Date of Electronic Publication: 2010 Dec 21. - Publication Year :
- 2011
-
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.<br /> (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0023
- Volume :
- 53
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 21177120
- Full Text :
- https://doi.org/10.1016/j.cyto.2010.11.017