Interleukin-8/CXCL8 forms an autocrine loop in fetal intestinal mucosa

Akhil Maheshwari, Atilano Lacson, Wenge Lu, Samuel E. Fox, Aaron A. Barleycorn, Robert D. Christensen, Darlene A. Calhoun

Research output: Contribution to journalArticle

Abstract

IL-8/CXC ligand (CXCL) 8 is ingested in high concentrations by the human fetus/neonate with amniotic fluid and human milk, and is also produced constitutively by intestinal epithelial cells (IEC). We have shown that recombinant human IL-8/CXCL8 (rhIL-8/CXCL8) protects cultured IEC against tumor necrosis factor (TNF)-α and cycloheximide-induced cytotoxicity. In view of its constitutive production, we hypothesized that IL-8/CXCL8 might play an autocrine role in fetal enterocyte maintenance. In this study, we measured IL-8/CXCL8 mRNA concentrations in fetal intestine (11-22 wk gestation), sought the presence of the protein by immunohistochemistry in fetal stomach and intestine (9-24 wk), measured IL-8/CXCL8 in neonatal gastric secretions, and studied constitutive and stimulated IL-8/CXCL8 expression in cultured IEC. We found that IL-8/CXCL8 is consistently transcribed and expressed in fetal intestinal tissue, in a developmentally regulated inverse relationship with gestational maturation. The cognate receptors for IL-8/CXCL8 are also expressed abundantly in the fetal intestine, and, therefore, we sought to determine whether the expressed IL-8/CXCL8 would complete an autocrine loop. Neutralization of IL-8/CXCL8 resulted in increased cell death in cultured IEC in the presence of TNF-α. This effect is specifically mediated through the CXCR2 receptors. We speculate that IL-8/CXCL8 secretion during cytotoxic stress reflects a cellular self-defense mechanism.

Original languageEnglish (US)
Pages (from-to)240-249
Number of pages10
JournalPediatric Research
Volume56
Issue number2
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

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Intestinal Mucosa
Interleukin-8
Epithelial Cells
Intestines
Stomach
Fetus
Interleukin-8B Receptors
Tumor Necrosis Factor-alpha
Interleukin-8 Receptors
Enterocytes
Human Milk
Amniotic Fluid
Cycloheximide
Cell Death
Immunohistochemistry
Maintenance
Ligands
Pregnancy
Messenger RNA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Maheshwari, A., Lacson, A., Lu, W., Fox, S. E., Barleycorn, A. A., Christensen, R. D., & Calhoun, D. A. (2004). Interleukin-8/CXCL8 forms an autocrine loop in fetal intestinal mucosa. Pediatric Research, 56(2), 240-249. https://doi.org/10.1203/01.PDR.0000133196.25949.98

Interleukin-8/CXCL8 forms an autocrine loop in fetal intestinal mucosa. / Maheshwari, Akhil; Lacson, Atilano; Lu, Wenge; Fox, Samuel E.; Barleycorn, Aaron A.; Christensen, Robert D.; Calhoun, Darlene A.

In: Pediatric Research, Vol. 56, No. 2, 01.08.2004, p. 240-249.

Research output: Contribution to journalArticle

Maheshwari, A, Lacson, A, Lu, W, Fox, SE, Barleycorn, AA, Christensen, RD & Calhoun, DA 2004, 'Interleukin-8/CXCL8 forms an autocrine loop in fetal intestinal mucosa', Pediatric Research, vol. 56, no. 2, pp. 240-249. https://doi.org/10.1203/01.PDR.0000133196.25949.98
Maheshwari, Akhil ; Lacson, Atilano ; Lu, Wenge ; Fox, Samuel E. ; Barleycorn, Aaron A. ; Christensen, Robert D. ; Calhoun, Darlene A. / Interleukin-8/CXCL8 forms an autocrine loop in fetal intestinal mucosa. In: Pediatric Research. 2004 ; Vol. 56, No. 2. pp. 240-249.
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