Introduction
a basic, histidine-rich, keratin
filament-aggregating protein synthesized by cells of
keratinizing epithelia, that subserves major physiological
functions in maturating epidermis.
PMID: 3125677,
PMID: 6187370
an intermediate filament-associated protein
(IFAP) that aggregates epidermal keratin filaments in vitro and
is thought to perform a similar function during terminal
differentiation in vivo.
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a component of cornified cell envelopes in
human plantar epidermis.
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a key protein that facilitates terminal
differentiation of the epidermis and formation of the skin
barrier.
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filaggrin can disrupt the distribution of
desmosome proteins, suggesting an additional role(s) for this
protein in the cytoskeletal and desmosomal reorganization that
occurs at the granular to cornified cell transition during
terminal differentiation of epidermal keratinocytes.
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filaggrin aids in the terminal
differentiation process by facilitating apoptotic machinery.
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PMID: 9008231
Normal Expression
primarily expressed in the granular cells of
the epidermis and in the inner root sheath cells of the hair
follicles, respectively.
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present in the granular and horny layers of
normal epidermis.
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present in the stratum granulosum which had
variable thickness.
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Normal squamous cervical epithelium exhibited
a positive homogeneous immunoperoxidase stain in the upper
parabasal, intermediate and superficial cell layers.
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localization of filaggrin in lower cornified
cells correlates precisely with the formation of aggregated
keratin filaments, and the disappearance of filaggrin in upper
cornified cells correlates precisely with the loosening of
keratin filaments.
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Diseased Expression
Filaggrin was intensely detected in the
granular layer in the cyst wall of dermoid cysts (DC).
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expressed in the cornified layer of epidermis
and known to be one of the antigenic targets in rheumatoid
arthritis.
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CCP2 can replace other anti-filaggrin
antibodies and improve rheumatoid arthritis diagnosis.
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Expression Alteration
Filaggrin expression was elevated in
reepithelialized epithelium during human cutaneous wound
healing.
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calcitriol alters expression of filaggrin but
not keratin K1 in mouse epidermis.
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Acute or chronic topical retinoic acid
treatment of human skin in vivo alters the expression of
epidermal transglutaminase, loricrin, involucrin, filaggrin, and
keratins 6 and 13 but not keratins 1, 10, and 14.
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TPA induces the synthesis of histidine-rich
protein (filaggrin) in monolayer cultures of rat keratinocytes.
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Applications
ELISA
sera were tested with enzyme linked
immunosorbent assays (ELISAs), using filaggrin purified from
human skin and citrullinated cyclic peptide (CCP) as antigens.
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Antifilaggrin autoantibodies were detected by
an ELISA using a recombinant rat filaggrin deiminated in vitro
as immunosorbent (ArFA-ELISA).
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A simple and easily standardisable ELISA for
detection of antifilaggrin autoantibodies was developed and
validated on a large series of patients using a citrullinated
recombinant human filaggrin.
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Filaggrin was used as antigen in
enzyme-linked immunosorbent assay (ELISA) to measure IgG class
antifilaggrin antibodies.
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the amount of filaggrin in the skin of the
inner surface of the upper arm of AD patients (nonlesional skin)
and normal controls, obtained by punch biopsy, was measured by
an enzyme-linked immunosorbent assay (ELISA) technique.
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Electron Microscopy
Immunoelectron microscopy demonstrated the
distinct intracellular distribution of filaggrin and
trichohyalin.
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An immunoelectron microscopy analysis showed
specific binding of four different anti-(pro)filaggrin
monoclonal antibodies to the surface of the CE, proved
previously to be free of non-covalently linked proteins.
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Using immunoelectron microscopy we found that
the majority of the granules, which are basophilic, are strongly
reactive to an anti-filaggrin antibody, while the minority,
which are eosinophilic, are not.
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immuno-electron microscopy was used to
localize filaggrin and its cross-reactive precursor,
profilaggrin, in human and mouse epidermis, as well as in
ichthyosis vulgaris epidermis.
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Skin biopsies of ridged and non-ridged skin
of normal individuals and patients with autosomal dominant
ichthyosis vulgaris (ADI)--characterized by defective
keratohyalin synthesis and lack of filaggrin--were investigated
by routine transmission electron microscopy and immunogold
postembedding techniques using a commercial monoclonal anti-filaggrin
antibody.
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Immunofluorescence
seven monoclonal antibodies, against
epidermal filaggrin (AHF1-7), were characterized on human
epidermis by indirect immunofluorescence, immunogold labeling,
and immunoblotting and found to be directed against seven
different epitopes of (pro)filaggrin.
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This investigation was carried out on frozen
sections using indirect immunofluorescence for filaggrin
detection.
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Localization of filaggrin, a human epithelial
structural protein, was investigated by indirect-immunofluorescence
microscopy of oral mucosa.
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Immunohistochemistry
immunohistochemical studies were performed on
trichohyalin and its related proteins, filaggrin and involucrin,
the components of the cornified cell envelope.
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Epidermal filaggrin expression was determined
using immunohistochemical techniques and Western blot in 12
patients with LI and the findings were compared with those
observed in four normal controls and eight patients with
ichthyosis vulgaris.
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epidermal proteins filaggrin, involucrin,
cystatin A and Ted-H-1 antigen produced during the terminal
differentiation of keratinocytes were immunohistochemically
measured in lesional and nonlesional skin of atopic dermatitis
(AD) patients.
PMID: 8844122
Immunohistochemical staining showed an
increased number of filaggrin-immunoreactive cell layers, but
the reaction was still confined to the mid- and upper epidermal
layers, whereas an abnormal granular pattern of staining for K10
began in the lower suprabasal cell layers. This suggests that
the aggregation of keratin filaments precedes, and occurs
independently of, profilaggrin synthesis during epidermal
differentiation.
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Immunohistochemical localization of filaggrin
in benign, premalignant and malignant cervical tissue.
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Immunohistochemical localization of filaggrin
in benign and malignant lesions of the human oral mucosa.
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filaggrin expression in paraffin-embedded
biopsy specimens of extragenital Bowen's disease and genital
bowenoid papulosis.
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formalin-fixed paraffin-embedded biopsies of
various benign, premalignant and malignant skin tumours were
examined immunohistochemically for the presence of filaggrin
using the monoclonal anti-filaggrin antibody AKH1.
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Filaggrin, a histidine-rich protein, was
located immunohistochemically in human middle ear cholesteatoma
by specific antibody.
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An avidin-biotin-alkaline phosphatase
technique was applied on deparaffinized tissue sections, by
using a specific monoclonal antibody (AKH1) to profilaggrin/filaggrin.
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Two monoclonal antibodies (AKH1 and AKH2)
were elicited with partially purified human filaggrin and
characterized by immunohistochemistry on normal and abnormal
skin biopsies, immunoblotting techniques, and antigen
purification.
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The distribution pattern of filaggrin in
lesions of human oral mucosa was studied with the use of an
anti-filaggrin serum raised in rabbits using
immunohistochemistry.
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Western Blot
Epidermal filaggrin expression was determined
using immunohistochemical techniques and Western blot in 12
patients with LI and the findings were compared with those
observed in four normal controls and eight patients with
ichthyosis vulgaris.
PMID: 9990356
Antibodies to filaggrin were detected using
immunoblotting techniques with sera diluted 1:50.
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a new diagnostic test for rheumatoid
arthritis (RA) based on detection of antifilaggrin
autoantibodies (AFA) by immunoblotting.
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The major structural proteins of epithelia,
the keratins, and the keratin filament-associated protein,
filaggrin, were analyzed in more than 50 samples of human
embryonic and fetal skin by one-dimensional SDS PAGE and
immunoblotting with monoclonal and polyclonal antibodies.
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