TY - JOUR
T1 - UCHL1 /PGP 9.5 Dynamic in Neuro-Immune-Cutaneous Milieu
T2 - Focusing on Axonal Nerve Terminals and Epidermal Keratinocytes in Psoriatic Itch
AU - Kupczyk, Piotr
AU - Reich, Adam
AU - Gajda, Mariusz
AU - Hołysz, Marcin
AU - Wysokińska, Edyta
AU - Paprocka, Maria
AU - Nevozhay, Dmitry
AU - Chodaczek, Grzegorz
AU - Jagodziński, Paweł P.
AU - Ziółkowski, Piotr
AU - Szepietowski, Jacek C.
N1 - Funding Information:
All investigations were financially supported by “Preludium” grant from the Polish National Science Center (UMO-2011/01/N/NZ4/04946): “Gene and protein analysis of OPRM1/MOR and OPRK1/KOR opioid receptors expression and neurobiological marker of nerve terminals PGP 9.5 in skin of psoriasis patients with and without pruritus” realized in 2011–2013 years. Dmitry Nevozhay acknowledges support from the Ministry of Education and Science, Russian Federation, through Program 1326. The authors would like to extend special thanks to Dr. Mariusz Gajda for his excellent knowledge and technical support of peripheral nervous system and Dr. Marcin Hołysz for supporting all molecular biology procedures. Furthermore, they would like to specially thank Dr. Beata Nowakowska from Laboratory of Tissues Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy Medical Centre, Polish Academy of Sciences, for her organizational support and incredible kindness.
Publisher Copyright:
© 2018 Piotr Kupczyk et al.
PY - 2018
Y1 - 2018
N2 - Psoriasis is an immunogenetic skin disease manifesting as plaque lesions on the skin. Patients with psoriasis frequently suffer from itch, an unpleasant sensation causing a desire to scratch. Psoriatic itch is mainly transmitted by unmyelinated C-fibers; however, the exact molecular mechanism of psoriatic itch is still unexplained. Protein gene product 9.5 (PGP 9.5) is a panneurological marker commonly used for analysis of peripheral peptidergic and nonpeptidergic nerves and identification of cutaneous neuro-immune-endocrine cells. However, some studies suggested that nonneuronal cells, like keratinocytes, may also express PGP 9.5. This phenomenon might be linked with impaired axonal transport, keratinocyte injury, or dysfunctions of neuro-immune-cutaneous connections. The aim of this study was to analyze the expression of PGP 9.5 in psoriatic skin. We observed significantly altered density of PGP 9.5-positive axonal nerve terminals in pruritic lesional (p=0.04) and nonlesional psoriatic skin (p>0.001) compared with controls. In contrast, no significant differences were observed between psoriatic skin without itch and controls. Furthermore, PGP 9.5 expression by suprabasal keratinocytes (SBKs) was significantly increased in itchy skin lesions (p=0.007) compared to skin without itch, and a positive correlation was observed between PGP 9.5 expression and itch intensity (r=0.64; p=0.02). Our findings indicate changes in peripheral innervations and psoriatic keratinocytes, which may influence neuro-immune-cutaneous homeostasis and modulate itch transmission.
AB - Psoriasis is an immunogenetic skin disease manifesting as plaque lesions on the skin. Patients with psoriasis frequently suffer from itch, an unpleasant sensation causing a desire to scratch. Psoriatic itch is mainly transmitted by unmyelinated C-fibers; however, the exact molecular mechanism of psoriatic itch is still unexplained. Protein gene product 9.5 (PGP 9.5) is a panneurological marker commonly used for analysis of peripheral peptidergic and nonpeptidergic nerves and identification of cutaneous neuro-immune-endocrine cells. However, some studies suggested that nonneuronal cells, like keratinocytes, may also express PGP 9.5. This phenomenon might be linked with impaired axonal transport, keratinocyte injury, or dysfunctions of neuro-immune-cutaneous connections. The aim of this study was to analyze the expression of PGP 9.5 in psoriatic skin. We observed significantly altered density of PGP 9.5-positive axonal nerve terminals in pruritic lesional (p=0.04) and nonlesional psoriatic skin (p>0.001) compared with controls. In contrast, no significant differences were observed between psoriatic skin without itch and controls. Furthermore, PGP 9.5 expression by suprabasal keratinocytes (SBKs) was significantly increased in itchy skin lesions (p=0.007) compared to skin without itch, and a positive correlation was observed between PGP 9.5 expression and itch intensity (r=0.64; p=0.02). Our findings indicate changes in peripheral innervations and psoriatic keratinocytes, which may influence neuro-immune-cutaneous homeostasis and modulate itch transmission.
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U2 - 10.1155/2018/7489316
DO - 10.1155/2018/7489316
M3 - Article
C2 - 30148172
AN - SCOPUS:85051334694
SN - 2314-6133
VL - 2018
JO - BioMed research international
JF - BioMed research international
M1 - 7489316
ER -