Identification of a novel cytokine, ML-1, and its expression in subjects with asthma

M. Kawaguchi, L. F. Onuchic, X. D. Li, D. M. Essayan, J. Schroeder, H. Q. Xiao, M. C. Liu, G. Krishnaswamy, G. Germino, S. K. Huang

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Abstract

A novel gene, designated ML-1, was identified from a human genomic DNA clone and human T cell cDNA sequences. The second exon of ML-1 gene shares significant sequence identity with the gene encoding IL-17 (IL-17). ML-1 gene expression was upregulated in activated PBMCs, CD4+ T cells, allergen-specific Th0, Th1, and Th2 clones, activated basophils, and mast cells. Increased expression of the ML-1 gene, but not IL-17, was seen following allergen challenge in four asthmatic subjects, suggesting its role in allergic inflammatory responses. ML-1 from transiently transfected COS-7 cells was able to induce gene expression and protein production for IL-6 and IL-8 (at 10 ng/ml of ML-1: For IL-6, 599.6 ± 19.1 pg/ml; for IL-8, 1724.2 ± 132.9 pg/ml; and at 100 ng/ml of ML-1: For IL-6, 1005.3 ± 55.6 pg/ml; for IL-8, 4371.4 ± 280.5 pg/ml; p < 0.05 for both doses vs baseline) in primary bronchial epithelial (PBE) cells. Furthermore, increased expression of ICAM-1 was found in ML-1-stimulated PBE cells (mean fluorescence intensity (MFI) = 31.42 ± 4.39 vs baseline, MFI = 12.26 ± 1.77, p < 0.05), a functional feature distinct from IL-17 (MFI = 11.07 ± 1.22). This effect was not inhibited by a saturating amount of IL-17. These findings demonstrate that ML-1 is a novel cytokine with a distinct function, and suggest a different receptor for ML-1 on PBE cells.

Original languageEnglish
Pages (from-to)4430-4435
Number of pages6
JournalJournal of Immunology
Volume167
Issue number8
DOIs
Publication statusPublished - Oct 15 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Kawaguchi, M., Onuchic, L. F., Li, X. D., Essayan, D. M., Schroeder, J., Xiao, H. Q., Liu, M. C., Krishnaswamy, G., Germino, G., & Huang, S. K. (2001). Identification of a novel cytokine, ML-1, and its expression in subjects with asthma. Journal of Immunology, 167(8), 4430-4435. https://doi.org/10.4049/jimmunol.167.8.4430