000			03010nam a2200373Ia 4500
003			MX-MdCICY
005			20250625160200.0
040			_cCICY
090			_aB-16895
245	1	0	_aMice that express human interleukin-8 have increased mobilization of immature myeloid cells, which exacerbates inflammation and accelerates colon carcinogenesis
490	0		_vGastroenterology, 144(1), p.155-166, 2013
520	3		_aBackground Aims: Interleukin (IL)-8 has an important role in initiating inflammation in humans, attracting immune cells such as neutrophils through their receptors CXCR1 and CXCR2. IL-8 has been proposed to contribute to chronic inflammation and cancer. However, mice do not have the IL-8 gene, so human cancer cell lines and xenograft studies have been used to study the role of IL-8 in colon and gastric carcinogenesis. We generated mice that carry a bacterial artificial chromosome that encompasses the entire human IL-8 gene, including its regulatory elements (IL-8Tg mice). Methods: We studied the effects of IL-8 expression in APCmin+/- mice and IL-8Tg mice given azoxymethane and dextran sodium sulfate (DSS). We also examined the effects of IL-8 expression in gastric cancer in INS-GAS mice that overexpress gastrin and IL-8Tg mice infected with Helicobacter felis. Results: In IL-8Tg mice, expression of human IL-8 was controlled by its own regulatory elements, with virtually no messenger RNA or protein detectable under basal conditions. IL-8 was strongly up-regulated on systemic or local inflammatory stimulation, increasing mobilization of immature CD11b+Gr-1+ myeloid cells (IMCs)with thioglycolate-induced peritonitis, DSS-induced colitis, and H. felis-induced gastritis. IL-8 was increased in colorectal tumors from patients and IL-8Tg mice compared with nontumor tissues. IL-8Tg mice developed more tumors than wild-type mice following administration of azoxymethane and DSS. Expression of IL-8 increased tumorigenesis in APCmin+/- mice compared with APCmin+/- mice that lack IL-8; this was associated with increased numbers of IMCs and angiogenesis in the tumors. Conclusions: IL-8 contributes to gastrointestinal carcinogenesis by mobilizing IMCs and might be a therapeutic target for gastrointestinal cancers.
650	1	4	_aCOLON CANCER
650	1	4	_aGASTRIC CANCER
650	1	4	_aIMMUNE REGULATION
650	1	4	_aMOUSE MODEL
700	1	2	_aAsfaha, S.
700	1	2	_aDubeykovskiy, A.N.
700	1	2	_aTomita, H.
700	1	2	_aYang, X.
700	1	2	_aStokes, S.
700	1	2	_aShibata, W.
700	1	2	_aFriedman, R.A.
700	1	2	_aFriedman, R.A.
700	1	2	_aDubeykovskaya, Z.A.
700	1	2	_aMuthupalani, S.
700	1	2	_aEricksen, R.
700	1	2	_aFrucht, H.
700	1	2	_aFox, J.G.
700	1	2	_aWang, T.C.
856	4	0	_uhttps://drive.google.com/file/d/1H8E7Kummz7Ao_acHO67tXtwFFJcy9wUr/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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