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PMID: 1386612 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Interleukin-1 receptor antagonist in normal and psoriatic epidermis.

The Journal of clinical investigation ·Vol. 90 ·No. 2 ·1992-08-00 ·Pages 571-83

Hammerberg C, Arend WP, Fisher GJ, Chan LS, Berger AE, Haskill JS, Voorhees JJ, Cooper KD

Abstract

The objective of these studies was to characterize the IL-1 inhibitory activity present in normal and psoriatic epidermis from clinically stable lesions. Fractionation of normal epidermal cytosol on a molecular sizing column failed to reveal the presence of IL-1 inhibitory bioactivity. However, specific ELISAs indicated that both the IL-1 receptor antagonist (IL-1ra) and IL-1 alpha were present in overlapping peaks. Further fractionation of the normal epidermal cytosol by anion exchange chromatography separated these two molecules, revealing the IL-1 inhibitory bioactivity of the IL-1ra molecule. Similar studies on psoriatic epidermal cytosol indicated the presence of IL-1 inhibitory bioactivity and IL-1ra protein. The IL-1 inhibitory bioactivity of both normal and psoriatic cytosol was neutralized by a mAb specific for IL-1ra. The ratio of IL-1ra to IL-1 alpha proteins was significantly increased in involved psoriatic skin compared with normal skin. By Western blot analysis this IL-1ra was approximately 20 kD, slightly larger than monocyte-derived IL-1ra and equivalent to an intracellular variant of IL-1ra expressed by keratinocytes. Polymerase chain reaction indicated the presence of mRNA for both forms of IL-1ra in normal epidermis, with both forms increased in psoriatic-involved skin. Immunofluorescence studies revealed the IL-1ra protein to be concentrated in the stratum granulosum of normal skin and in the basal-midbasal layers of psoriatic epidermis. These results suggest that the balance between intracellular IL-1ra and IL-1 alpha may be an important influence on keratinocyte growth and/or differentiation, as well as on the inflammatory potential of IL-1 in injured skin.

MeSH Terms
Antibodies, Monoclonal Cytosol/metabolism Epidermis/metabolism Fluorescent Antibody Technique Gene Expression Humans Interleukin 1 Receptor Antagonist Protein Interleukin-1/metabolism Molecular Weight Proteins/chemistry,immunology,metabolism Psoriasis/metabolism RNA, Messenger/genetics Receptors, Immunologic/antagonists & inhibitors Receptors, Interleukin-1 Sialoglycoproteins
Chemicals
Antibodies, Monoclonal IL1RN protein, human Interleukin 1 Receptor Antagonist Protein Interleukin-1 Proteins RNA, Messenger Receptors, Immunologic Receptors, Interleukin-1 Sialoglycoproteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Hammerberg C
Department of Dermatology, University of Michigan Medical School, Ann Arbor 48109-0530.
Arend W P
Fisher G J
Chan L S
Berger A E
Haskill J S
Voorhees J J
Cooper K D
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115896
Published
1992-08-00
Pages
571-83
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC443136
Subset
IM
Grants
NIAMS NIH HHS · AR01770 · United States
NIAMS NIH HHS · AR39950 · United States
NIAMS NIH HHS · AR40135 · United States
External Links
PubMed source DOI: 10.1172/JCI115896 PMC Full Text View journal details
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