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interleukin-18 (IL18) 412 interleukin-19 (IL19)
upregulated in inflammatory responses. IL17B is expressed
in immune tissues and IL17C is upregulated in inflammation.
IL17D is expressed in the nervous system and skeletal
muscle tissue. IL17E is expressed at low levels in various
peripheral tissues. IL17 was shown to be dependent on
IL23. STAT3 and NF-κB signaling are required for IL23mediated
IL17 synthesis. SOCS3 has a significant role in
IL17 synthesis. Whether IL17 induction is dependent on
IL23 or not, IL23 is important in promoting survival and/or
proliferation of IL17-synthesizing T cells. A 155-amino acid
protein, IL17A is a disulfide-linked, homodimeric-secreted
glycoprotein. The molecular mass is 35 kDa. The homodimer
subunits range from 15 to 20 kDa. IL17 is comprised of
a single peptide of 23 amino acids followed by a 123-amino
acid chain region that is a feature of the IL17 family. It has
an N-linked glycosylation site. IL17 family members contain
four conserved cysteines that form two disulfide bonds.
IL17 is dissimilar from all other interleukins, and bears no
resemblance to other known proteins or structural domains.
Five receptors with unique ligand specificities comprise
the IL17 receptor family. IL17R interacts with both IL17A
and IL17F and is expressed by vascular endothelial cells,
peripheral T cells, B cells, fibroblasts, lung, myelomonocytic
cells, and marrow stromal cells. IL17RB interacts
with both IL17B and IL17E. Kidney, pancreas, brain, liver,
and intestine express IL17RB, whereas prostate, cartilage,
kidney, liver, heart, and muscle express IL17RC. Pancreas,
brain, and prostate express IL17RE. Identification and
characterization of IL12 and IL17 cytokine family members
have elucidated a new arm of the adaptive immune
response known as Th17 and a significant new player in
the Th2 arm. Th17 responses are controlled by IL12 family
cytokines, IL23, IL27, IL6, prototype for IL12 cytokines,
and innate immune cell products. IL6 is a principal danger
signal that switches the proregulatory TGF-β cytokine into
a Th17-diverting mediator, making it a principal cytokine
in self–nonself discrimination. The discovery of IL17
cytokines and the Th17 pathway has important implications
for treating human diseases. IL23- and IL17-targeting treatments
should prove highly effective in controlling certain
autoinflammatory disorders.
Interleukin-18.
interleukin-18 (IL18)
A proinflammatory cytokine synthesized by macrophages
and other cells that belongs to the IL1 cytokine family
based on its structure, receptor family, and signal
transduction pathways. It functions with IL12 to induce
cell-mediated immunity in the defense against intracellular
bacteria including Listeria, Shigella, Salmonella, and
Mycobacterium tuberculosis. As with IL1β, IL18 is synthesized
as a precursor requiring caspase-1 for cleavage into an
active IL18 molecule. With respect to its capacity to induce
synthesis of Th1 cytokines and enhance cell-mediated
cytotoxicity, IL18 is related to IL12. It is formed mainly by
antigen-presenting cells and is a pleiotropic factor involved
in the regulation of both innate and acquired immune
responses, playing a key role in autoimmune, inflammatory
and infectious diseases. Following stimulation by IL18, NK
cells and selected T cells release IF-γ that plays a significant
role in activating macrophages and other cells. The combination
of IL18 with IL12 inhibits IL4-dependent IgE and
IgG1 synthesis and facilitates IgG2a production by B cells.
IL18 binding protein (IL18BP) binds specifically with the
cytokine to negatively regulate its biological activity. With
IL12, IL18 stimulates Th1-mediated immune responses
critical for host defense against infection with intracellular
microbes through the induction of IFN-γ. IL18 is a potent
proinflammatory cytokine, since overproduction of IL12 and
IL18 induces severe inflammatory disorders. IL18 enhances
IL12-driven Th1 immune responses, but it can also stimulate
Th2 immune responses in the absence of IL12.
Interleukin-19 crystal structure.
interleukin-19 (IL19)
A novel homolog of IL10, with which it shares 21% amino
acid identity and thus belongs to the IL10 family along
with IL20, IL22, IL24, IL26, and several virus-encoded
cytokines. The expression of IL19mRMA can be induced
in monocytes by LPS treatment. GM-CSF can directly
induce IL19 gene expression by monocytes. IL19 shares a
receptor complex with IL20, indicating that the biological