RGD Reference Report - Substance P regulates natural killer cell interferon-gamma production and resistance to Pseudomonas aeruginosa infection. - Rat Genome Database

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Substance P regulates natural killer cell interferon-gamma production and resistance to Pseudomonas aeruginosa infection.

Authors: Lighvani, S  Huang, X  Trivedi, PP  Swanborg, RH  Hazlett, LD 
Citation: Lighvani S, etal., Eur J Immunol. 2005 May;35(5):1567-75.
RGD ID: 8157597
Pubmed: PMID:15832292   (View Abstract at PubMed)
DOI: DOI:10.1002/eji.200425902   (Journal Full-text)

Studies have shown that after Pseudomonas aeruginosa (P. aeruginosa) corneal infection, BALB/c mice that are capable of resolving the disease, locally produce IFN-gamma. As T cells are not detected in the infected cornea of these mice, antibody depletion was used to test whether NK cells produce the cytokine. After depletion, decreased corneal IFN-gamma mRNA and increased disease severity, bacterial load, and PMN infiltrate resulted. Further work determined if substance P (SP), a pro-inflammatory neuropeptide, participated in regulation of this response. To this end, mice were treated with the SP antagonist, spantide I that blocks SP interaction with neurokinin-1, its major receptor. The treatment significantly decreased corneal IFN-gamma and IL-18 protein levels and corneal perforation resulted. In vitro experiments using isolated splenic NK cells confirmed their ability to respond to IL-18 and SP and to secrete IFN-gamma protein. We conclude: that for development of the BALB/c resistance response, NK cells are required to produce IFN-gamma; that the cells express the neurokinin-1 receptor; and that SP directly regulates IFN-gamma production through this receptor. The data suggest a unique link between the nervous system and development of innate immunity in the cornea.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Corneal Perforation  ISOIfng (Mus musculus)8157597; 8157597mRNA and protein:increased expression:cornealRGD 
Corneal Perforation  IEP 8157597mRNA and protein:increased expression:cornealRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ifng  (interferon gamma)

Genes (Mus musculus)
Ifng  (interferon gamma)

Genes (Homo sapiens)
IFNG  (interferon gamma)


Additional Information