Inhibition of Activin A suppressed tumor necrosis factor-α secretion and improved histopathological conditions in malarial mice
https://doi.org/10.47665/tb.38.1.018
- Author:
Chin, V.K.
1
,
2
;
Tie, T.H.
3
;
Abd Majid, R.
4
,
5
;
Hassan, H.
3
;
Nordin, N.
6
;
Abas, R.
3
;
Basir, R.
3
Author Information
1. Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia&
2. Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi Mara, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia
3. Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
4. Preclinical Department, Faculty of Medicine &
5. Health Defence, National Defence University of Malaysia, Kem Sungai Besi, 57000 Kuala Lumpur, Malaysia
6. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
- Publication Type:Journal Article
- Keywords:
Activin A;
malaria pathogenesis;
tumor necrosis factor-α (TNF-α);
histopathological
- From:Tropical Biomedicine
2021;38(No.1):187-204
- CountryMalaysia
- Language:English
-
Abstract:
Malaria infection still remains as one of the most prominent parasitic diseases afflicting
mankind in tropical and subtropical regions. The severity of malaria infection has often
been associated to exuberant host immune inflammatory responses that could possibly
lead to severe immunopathological conditions and subsequent death of host tissues. Activin
A is a protein belonging to the transforming growth factor-beta (TGF-β) family that regulates
multiple physiological processes and pathological-associated diseases. The biological
roles of activin A have been associated with manipulation of inflammation-related processes
and modulation of host immune responses. This implies that activin A protein could play a
role in malaria pathogenesis since malaria infection has been closely linked to severe
immune responses leading to death, However, the actual in vivo role of activin A in malaria
infection remains elusive. Hence, this study was undertaken to investigate the involvement
of activin A in malaria infection as well as to assess the modulating effects of activin A on
the cytokine releases (TNF-α, IFN-γ and IL-10) and histopathological changes in major affected
organs (kidney, liver, lung, brain and spleen) in malarial mice infected with Plasmodium
berghei ANKA. Our results showed that the concentrations of plasma activin A were significantly
increased in malarial mice throughout the study periods. Also. the systemic activin A level
was positively correlated with malaria parasitemia. This indicates that activin A could play
a role in malaria pathogenesis and malaria parasitemia development. Plasma TNF-α,
IFN-γ and IL-10 cytokine levels were significantly increased in malarial mice at day-5 post
infection, suggesting that these cytokines attributed to severe malaria pathogenesis.
Histopathological features such as sequestration of parasitized red blood cells (pRBCs)
and hemozoin formation were amongst the most common pathological conditions observed
in tissues of major affected organs (kidney, liver, lung, brain and spleen) in malarial mice.
Neutralization of activin A production via recombinant mouse activin RIIA Fc chimera (rmActivin
RIIA Fc chimera) had significantly reduced the parasitemia levels in malarial mice. The
release of TNF-α cytokine was significantly reduced as well as the sequestration of
parasitized pRBCs and hemozoin formation in major affected organs in malarial mice were
also alleviated following inhibition of activin A production. Overall, this preliminary study
suggests that activin A could play an immune modulation role in malaria pathogenesis
through modulation of TNF-α release that benefits host from severe pathological destructions
provoked by intensified inflammatory responses. Further studies are warranted to elucidate
the precise mechanism of immune modulation mediated by activin A and its associated
immune-modulation mediators in regulating the inflammatory responses elicited during
the course of malaria infection.
- Full text:8.2021my1230.pdf
