Identification of a novel cytokine, ML-1, and its expression in subjects with asthma.
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 up-regulated 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.
Kawaguchi
M
M
Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Onuchic
L F
LF
Li
X D
XD
Essayan
D M
DM
Schroeder
J
J
Xiao
H Q
HQ
Liu
M C
MC
Krishnaswamy
G
G
Germino
G
G
Huang
S K
SK
D000595:Amino Acid Sequence; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000235:genetics / Q000302:isolation & purification; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000276:immunology; D011058:Pollen / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D016207:Cytokines; C440021:IL17F protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D010940:Plant Proteins; D018799:Intercellular Adhesion Molecule-1