RGD Reference Report - Macrophage-activating lipopeptide-2 (MALP-2) induces a localized inflammatory response in rats resulting in activation of brain sites implicated in fever. - Rat Genome Database

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Macrophage-activating lipopeptide-2 (MALP-2) induces a localized inflammatory response in rats resulting in activation of brain sites implicated in fever.

Authors: Knorr, C  Hubschle, T  Murgott, J  Muhlradt, P  Gerstberger, R  Roth, J 
Citation: Knorr C, etal., Brain Res. 2008 Apr 18;1205:36-46. Epub 2008 Feb 21.
RGD ID: 5684896
Pubmed: PMID:18353287   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2008.02.021   (Journal Full-text)

Macrophage-activating lipopeptide-2 (MALP-2) has been identified as the pathogen-associated molecular pattern of Mycoplasma fermentans, which causes stimulation of the innate immune system through the activation of the heterodimeric Toll-like receptors (TLRs) 2 and 6. Based on the reported protective effects of MALP-2 on healing of skin wounds, the central goal of this study was to evaluate the capacity of MALP-2 to induce a localized inflammatory response in an established model of a subcutaneous air pouch. Injections of MALP-2 into the pouch caused fever and some components of sickness behavior in rats. At the subcutaneous site of localized inflammation, a massive formation of tumor necrosis factor-alpha (TNF), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) could be demonstrated in response to injections of MALP-2. Moderate amounts of IL-6 and PGE2 seemed to enter the systemic circulation of MALP-2-treated rats. The IL-6, which appeared in the blood after injection of MALP-2 into the air pouch was sufficient to cause a direct activation of brain cells in areas which lack a complete blood-brain barrier, namely in the sensory circumventricular organs (sCVOs), the organum vasculosum laminae terminalis (OVLT), the subfornical organ (SFO), and the area postrema (AP). The stimulation of cells at these brain sites was revealed by demonstration of a nuclear translocation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Corresponding to the circulating levels of IL-6, the nuclear STAT3 activation of cells within the sCVOs was much less pronounced after local subcutaneous when compared to systemic treatment with MALP-2. In conclusion, cells within the subcutaneous compartment are activated by the TLR2/6 agonist MALP-2. Fever and sickness behavior induced by injection of MALP-2 into subcutaneous tissue may, in part, be mediated by a spillover of IL-6 from the subcutaneous site of inflammation into the blood to cause activation of brain sites which are implicated in the manifestation of these illness responses.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Tlr2Rattoll-like receptor signaling pathway  IMP  RGD 
Tlr6Rattoll-like receptor signaling pathway  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Tlr2Ratlipopeptide binding  IMP  RGD 
Tlr6Ratlipopeptide binding  IMP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Objects Annotated

Genes (Rattus norvegicus)
Tlr2  (toll-like receptor 2)
Tlr6  (toll-like receptor 6)

Genes (Mus musculus)
Tlr2  (toll-like receptor 2)
Tlr6  (toll-like receptor 6)

Genes (Homo sapiens)
TLR2  (toll like receptor 2)
TLR6  (toll like receptor 6)


Additional Information