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2017 ; 6
(10
): e157
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Suppression of inflammation and tissue damage by a hookworm recombinant protein
in experimental colitis
#MMPMID29114386
Ferreira IB
; Pickering DA
; Troy S
; Croese J
; Loukas A
; Navarro S
Clin Transl Immunology
2017[Oct]; 6
(10
): e157
PMID29114386
show ga
Gastrointestinal parasites, hookworms in particular, have evolved to cause
minimal harm to their hosts when present in small numbers, allowing them to
establish chronic infections for decades. They do so by creating an
immunoregulatory environment that promotes their own survival, but paradoxically
also benefits the host by protecting against the onset of many inflammatory
diseases. To harness the therapeutic value of hookworms without using live
parasites, we have examined the protective properties of the recombinant protein
anti-inflammatory protein (AIP)-1, secreted in abundance by hookworms within the
intestinal mucosa, in experimental colitis. Colitic inflammation assessed by
weight loss, colon atrophy, oedema, ulceration and necrosis, as well as abdominal
adhesion was significantly suppressed in mice treated with a single
intraperitoneal dose of AIP-1 at 1?mg?kg(-1). Local infiltration of inflammatory
cells was also significantly reduced, with minimal goblet cell loss and preserved
mucosal architecture. Treatment with AIP-1 promoted the production of colon
interleukin (IL)-10, transforming growth factor (TGF)-? and thymic stromal
lymphopoietin (TSLP), resulting in the suppression of tumour necrosis factor
(TNF)-?, IL-13 and IL-17?A cytokines and granulocyte macrophage
colony-stimulating factor (GM-CSF), CX motif chemokine (CXCL)-11 and
cyclooxygenase synthase (COX)-2 mRNA transcripts. AIP-1 promoted the accumulation
of regulatory T cells in the colon likely allowing rapid healing of the colon
mucosa. Hookworm recombinant AIP-1 is a novel therapeutic candidate for the
treatment of inflammatory bowel diseases that can be explored for the prevention
of acute inflammatory relapses, an important cause of colorectal cancer.