TY - JOUR
TI - Luteolin Inhibits Human Keratinocyte Activation and Decreases NF-kappa B
Induction That Is Increased in Psoriatic Skin
AU - Weng, Zuyi
AU - Patel, Arti B.
AU - Vasiadi, Magdalini
AU - Therianou,
AU - Anastasia
AU - Theoharides, Theoharis C.
JO - PLOS ONE
PY - 2014
VL - 9
TODO - 2
SP - null
PB - Public Library of Science
SN - null
TODO - 10.1371/journal.pone.0090739
TODO - null
TODO - Psoriasis (Ps) is an autoimmune disease characterized by keratinocyte
hyperproliferation and chronic inflammation, with increased expression
of tumor necrosis factor (TNF) and vascular endothelial growth factor
(VEGF). Anti-TNF biologic agents are effective in treating Ps, but are
associated with increased risk of infections and blood malignancies.
Moreover, keratinocyte hyperproliferation and activation have yet to be
addressed. Flavonoids, such as luteolin, are natural compounds with
potent anti-inflammatory properties, but their actions on keratinocytes
remain unknown. We show that TNF (50 ng/mL) triggers significant
production of inflammatory mediators interleukin-6, interleukin-8 and
VEGF from both human HaCaT and primary keratinocytes. Pretreatment with
the flavonoid luteolin (10-100 mu M) significantly inhibits mRNA
expression and release of all three mediators in a
concentration-dependent manner. More importantly, luteolin decreases
TNF-induced phosphorylation, nuclear translocation and DNA binding of
the nuclear factor-kappa B (NF-kappa B) typically involved in
inflammatory mediator transcription. We also report that luteolin
reduces TNF-induced mRNA expression of two genes (NFKB1 and RELA)
encoding two NF-kappa B subunits (NF-kappa B p50 and NF-kappa B p65,
respectively). Interestingly, we show that gene expression of RELA is
increased in human psoriatic skin. Keratinocyte proliferation, which is
a characteristic feature of psoriatic skin, is effectively reduced by
luteolin in HaCaT cells, but not in primary keratinocytes. Finally,
luteolin does not affect intracellular ATP production or viability.
Appropriate formulations of luteolin and related flavones may be
promising candidates to be developed into local and systemic treatments
for Ps and other inflammatory skin diseases.
ER -