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cytokeratin 7 (K72), mouse 208 cytokine
cytokeratin 7 (K72), mouse
Anticytokeratin 7 (K72) mouse monoclonal antibody reacts
with proteins that are found in most ductal, glandular
and transitional epithelium of the urinary tract and bile
duct epithelial cells. Cytokeratin 7 distinguishes between
lung and breast epithelia that stain positive and colon and
prostate epithelial cells that are negative. This antibody also
reacts with many benign and malignant epithelial lesions,
e.g., adenocarcinomas of the ovary, breast, and lung.
Transitional cell carcinomas are positive and prostate cancer
is negative. This antibody does not recognize intermediate
filament proteins.
cytokine
Leukocytes and other types of cells produce soluble
proteins or glycoproteins termed cytokines that serve as
chemical communicators between cells. Cytokines are
usually secreted, although some may be expressed on cell
membranes or maintained in reservoirs in the extracellular
matrix. Cytokines include proteins synthesized by
cells that affect the actions of other cells. They combine
with surface receptors on target cells that are linked to
intracellular signal transduction and second messenger
pathways. Their effects may be autocrine, acting on cells
that produce them, or paracrine, acting on neighboring
cells. Cytokines are immune system proteins that are biological
response modifiers. They coordinate antibody and
T cell immune system interactions and amplify immune
reactivity. Cytokines include monokines synthesized by
macrophages and lymphokines produced by activated
T lymphocytes and natural killer cells. A monokine is a
cytokine produced by monocytes. It is any one of a group
of biologically active factors secreted by monocytes and
macrophages that has a regulatory effect on the functions
of other cells such as lymphocytes. Monokines include
interleukin-1 (IL1), tumor necrosis factor (TNF), α and β
interferons (IFNs), and colony-stimulating factors (CSFs).
A lymphokine is a nonimmunoglobulin polypeptide substance
synthesized mainly by T lymphocytes that affects
the functions of other cells. It may enhance or suppress
an immune response. Lymphokines may facilitate cell
proliferation, growth, and differentiation, and they may
act on gene transcription to regulate cell function. They
exert paracrine or autocrine effects. Many lymphokines
have now been described. Well known examples include
IL2, IL3, migration inhibitory factor (MIF), and INF-γ.
The term cytokines includes lymphokines, soluble products
produced by lymphocytes, as well as mokines and
soluble products produced by monocytes. Lymphokines
include IL2 and IL6, INF-γ, granulocyte–macrophage
colony-stimulating factor (GM-CSF) and lymphotoxin.
MIF, endothelial cells, fibroblasts, and selected other
cell types may also synthesize cytokines. Lymphokine
research can be traced to the 1960s, when macrophage
MIF was described; it is believed to be due to more than
one cytokine in lymphocyte supernatants. Lymphotoxin
was described in activated lymphocyte culture supernatants
in the late 1960s, and lympokines were recognized
as cell-free soluble factors formed when sensitized lymphocytes
respond to specific antigens. These substances
were considered responsible for cell-mediated immune
reactions. IL2 was described as T cell growth factor. TNF
was the first monocyte-/macrophage-derived cytokine
or monokine to be recognized. Other cytokines derived
from monocytes include lymphocyte activation factor
(LAF), later named interleukin 1 (IL1). It was found to
be mitogenic for thymocytes. Immunologists described
lymphokines and monokines; virologists described interferons.
Interferon is a factor formed by virus-infected cells
that are able to induce resistance of cells to infection with
homologous or heterologous viruses. Subsequently, IFN-γ,
synthesized by T lymphocytes activated by mitogen, was
found to be distinct from IFN-α and IFN-β and to be
formed by a variety of cell types. CSFs were described as
proteins capable of promoting proliferation and differentiation
of hematopoietic cells. CSFs promote granulocyte or
monocyte colony formation in semisolid media. Proteins
that facilitate the growth of nonhematopoietic cells are not
usually included with cytokines. Transforming growth factor
β (TGF-β) has an important role in inflammation and
immunoregulation as well as immunosupressive actions on
T cells. Classes of cytokine receptors include the immunoglobin
receptor superfamily, the hematopoietic/cytokine
receptor superfamily, the nerve growth factor receptor
superfamily, the G protein-coupled receptor superfamily
and the other family, and the receptor tyrosine or serine
kinases plus an unclassified group. Cytokine receptor
families are classified according to conserved sequences
or folding motifs. Type I receptors share a tryptophan–
serine–X–tryptophan–serine (WSXWS) sequence on
the proximal extracellular domain. Type I receptors
recognize cytokines with a structure of four α-helical
strands, including IL2 and G-CSF. Type II receptors are
defined by the sequence patterns of type I and type II
interferon receptors. Type III serve as receptors for TNF.
CD40, nerve growth factor receptor, and Fas protein have
sequences homologous to those of type III receptors. A
fourth family of receptor has extracellular domains of the
immunoglobulin (Ig) superfamily. IL1 receptors as well as
some growth factors and colony-stimulating factors have
Ig domains. The fifth superfamily of receptors displays a
seven-transmembrane α-helical structure. This motif is
shared by many of the receptors linked to GTP-binding
proteins. A principal feature of cytokines is that their
effects are pleiotropic and redundant. Cytokines do not
exert a specific effect on one type of target cell. Most of
them have a broad spectrum of biological effects on more
than one type of tissue and cell. Various cytokines may
interact with the same cell type to produce similar effects.
Cytokine receptors are grouped into two classes. Class I
receptors include those that bind a number of interleukins,
including IL2, 3, 4, 6, 7, 9, 11, 12, and 15. Other type
I receptors are those for erythropoietin (EPO), growth
hormone (GH), granulocyte colony-stimulating factor
(G-CSF), granulocyte–macrophage colony-stimulating
factor (GM-CSF), leukemia inhibitory factor (LIF),
and ciliary neurotrophic factor (CNTF). Class II receptors
include those that bind IFN-α/β, IFN-γ, and IL10.
Cytokine receptors are usually comprised of multipeptide
complexes with a specific ligand-binding subunit and a
signal transducer subunit that is class-specific. Receptors
for IL3, IL5, and GM-CSF possess a unique a component
and a common b signal transducer subunit that account for
the redundant effects these molecules have on hematopoietic
cells. IL6, CNTF, LIF, oncostatin M (OM), and IL11