Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family.
IL-17 is a T cell-derived cytokine that may play an important role in the initiation or maintenance of the proinflammatory response. Whereas expression of IL-17 is restricted to activated T cells, the IL-17 receptor is found to be widely expressed, a finding consistent with the pleiotropic activities of IL-17. We have cloned and expressed two novel human cytokines, IL-17B and IL-17C, that are related to IL-17 ( approximately 27% amino acid identity). IL-17B mRNA is expressed in adult pancreas, small intestine, and stomach, whereas IL-17C mRNA is not detected by RNA blot hybridization of several adult tissues. No expression of IL-17B or IL-17C mRNA is found in activated T cells. In a survey of cytokine induction, IL-17B and IL-17C stimulate the release of tumor necrosis factor alpha and IL-1beta from the monocytic cell line, THP-1, whereas IL-17 has only a weak effect in this system. No induction of IL-1alpha, IL-6, IFN-gamma, or granulocyte colony-stimulating factor is found in THP-1 cells. Fluorescence-activated cell sorter analysis shows that IL-17B and IL-17C bind to THP-1 cells. Conversely, IL-17B and IL-17C are not active in an IL-17 assay or the stimulation of IL-6 release from human fibroblasts and do not bind to the human IL-17 receptor extracellular domain. These data show that there is a family of IL-17-related cytokines differing in patterns of expression and proinflammatory responses that may be transduced through a cognate set of cell surface receptors.
Li
H
H
Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Chen
J
J
Huang
A
A
Stinson
J
J
Heldens
S
S
Foster
J
J
Dowd
P
P
Gurney
A L
AL
Wood
W I
WI
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003001:Cloning, Molecular; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053722:Receptors, Interleukin-17; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D018076:DNA, Complementary; C109985:IL17RA protein, human; D007375:Interleukin-1; D020381:Interleukin-17; D020033:Protein Isoforms; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha