ISSN 10227954, Russian Journal of Genetics, 2014, Vol. 50, No. 10, pp. 1081–1089. © Pleiades Publishing, Inc., 2014.
Published in Russian in Genetika, 2014, Vol. 50, No. 10, pp. 1222–1231.
The social importance of psoriasis is enormous.
The statistical data revealed that approximately 1–2%
of the general population has psoriasis . The preva
lence of psoriasis in different populations varies dra
matically from 0.91% in the United States to 8.5% in
Norway . In the midland Russia, the disease rate is
about 1–2% . A lack of information on the psoriasis
etiology and absence of a cure for this disease make
pathogenesis of psoriasis one of the most desirable tar
gets in many experimental studies.
The development of psoriasis is mainly driven by
immune cells. In psoriatic plaques, the certain proin
flammatory cytokines, such as TNF, IFNG, and IL17
secreted by those cells activate the epidermal kerati
nocytes . The activation changes their terminal dif
ferentiation program and increases their proliferation
The experimental models that let us to imitate sep
arate aspects of the pathological process in controlled
conditions are often used to study psoriasis [5–7].
Presently, this approach became irreplaceable in pre
clinical studies of new medicines, especially in drug
screening. In basic research, the models are mainly
used to explore the molecular basis of the disease.
The article was translated by the authors.
There are three major types of experimental models:
cell lines, laboratory animals and three dimensional
skin models. Cells and animals are the most frequently
used. Threedimensional skin models represent artifi
cial imitations of skin created in a laboratory from one
or few kinds of propagated in vitro cells.
HaCaT cells are immortalized human kerati
nocytes. They are often used as an experimental model
to study psoriasis [8–10]. As an experimental model,
HaCaT cells have certain advantages compared to
both the primary epidermal keratinocytes and trans
formed cell lines. Unlike normal human epidermal
keratinocytes (NHEK), HaCaT cells are much easier
to culture. Culturing these cells does not require addi
tional supplements, such as growth factors. It also does
not require maintenance of the calcium concentration
at low level in the culture medium. HaCaT cells are
nontumorogenic. Their transplantation to lab ani
mals does not cause them any solid tumors. Moreover,
these cells differentiate normally and express in vivo
the common epidermal markers . On the other
hand, the transplanted HaCaT cells exhibit parakera
tosis, which is also one of hallmarks of psoriatic
Although HaCaT are frequently used as a model
system to study psoriasis, the influence of proinflam
matory cytokines on HaCaT proliferation rate has not
been previously studied. In this paper, we report that
Genetically Predetermined Limitation in HaCaT Cells that Affects
Their Ability to Serve as an Experimental Model of Psoriasis
A. G. Soboleva, A. D. Zolotarenko, V. V. Sobolev, S. A. Bruskin,
E. S. Piruzian, and A. V. Mezentsev
Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow
Received January 29, 2014
—Proinflammatory cytokines TNF, IFNG, and IL17 play an important role in eruption of psoriasis.
The activation of epidermal keratinocytes with the named cytokines alters their terminal differentiation pro
gram and causes their hyperproliferation in the diseased skin. HaCaT cells, which are immortalized human
keratinocytes, are often used as a cellular model of psoriasis. The aim of this study was to evaluate changes in
gene expression and the proliferation rates in cultured HaCaT cells treated with TNF, IFNG, and IL17. We
found that HaCaT cells decrease their proliferation rate in response to either IL17 or a combination TNF and
IFNG. The analysis of microarray data discovered a group of 12 genes, which were downregulated in HaCaT
after treatments with the named cytokines and upregulated in psoriatic lesional skin. Eight genes were impor
tant for DNA replication and they also contributed to two larger networks that regulated cell progression
through the cell cycle. We conclude that HaCaT cells have a sufficient limitation as a cellular model of psori
asis due to their treatment with proinflammatory cytokines, namely TNF, IFNG, and IL17 does not increase
their proliferation rate. Thus, the studies of psoriasis based on HaCaT cells as an experimental model shall
take in account this important phenomenon.