A comparison of neuropeptide expression in skin with allergic contact dermatitis in human and mouse.
BACKGROUND
Allergic contact dermatitis (ACD) is a manifestation of a cell-mediated immune response, but its mechanism remains unknown. Recently, we investigated whether ACD involves various neuropeptides. Substance P (SP) is a neuropeptide that is known to act as a neurokinin receptor when the immune response is initiated. Calcitonin gene-related peptide (CGRP) is a distinct typical neuropeptide and, with SP, induces the immune response. Neuropeptides in neurogenic inflammation are regulated by the inactivation of receptors and enzymes that can cause neuropeptide degradation (e.g. angiotensin-converting enzyme [ACE]), but no enzyme that can degrade SP and CGRP has yet been reported.


METHODS
We investigated changes in the expression of SP and CGRP, as representative of typical neuropeptides, in ACD skin in mouse and human and the effect of ACE expression on the degradation of these neuropeptides using reverse transcription polymerase chain reaction and immunoblot assay. We also examined the relationship between ACD and neuropeptides in skin tissue from human ACD subjects and mice with induced ACD by analyzing cytokine expression and the results of hematoxylin and eosin staining and immunofluorescence assay.


RESULTS
Expression of SP, CGRP, and ACE was higher in skin tissues from animals with acute ACD than in normal animal skin. However, CGRP expression in human skin with acute ACD was lower than in normal skin, unlike expression of SP and ACE, both of which were higher in ACD human skin than in normal human skin.


CONCLUSIONS
We found different patterns of neuropeptide expression in human versus mouse skin. These neuropeptide activities were influenced by an increase in neuropeptide degrading enzymes. Our findings show that when SP is produced, expression of CGRP is suppressed in human skin with ACD. The reduction of CGRP expression in patients with acute ACD is caused by mast cells activated by SP.
Department of Dermatology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Yun Young
YY
Lim
Hyeong Mi
HM
Kim
Hye In
HI
Lee
Seog-Kyun
SK
Mun
Chan Woong
CW
Kim
Myeung Nam
MN
Kim
Beom Joon
BJ
Kim
D000328:Adult; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis; D017449:Dermatitis, Allergic Contact / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013373:Substance P / Q000096:biosynthesis*; D055815:Young Adult
D016207:Cytokines; D013373:Substance P; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D015740:Calcitonin Gene-Related Peptide