Th2- and to a Lesser Extent Th1-Type Cytokines Upregulate the Production of both CXC (IL-8 and Gro-Alpha) and CC (RANTES, Eotaxin, Eotaxin-2, MCP-3 and MCP-4) Chemokines in Human Airway Epithelial Cells

Abstract

Background: Both CXC and CC chemokines play an important role in leukocyte recruitment. However, a systematic examination of their production by human airway epithelial cells (HAECs) has not been carried out. The objective of this study was to investigate whether Th1- and Th2-type cytokines regulate chemokine production in HAECs. Methods: HAECs were grown from both nasal and bronchial tissue and subsequently stimulated with either Th1- or Th2-type cytokines. Results: Constitutive mRNA expression for gro-alpha, IL-8 and RANTES was seen in both human nasal and human bronchial epithelial cells. IL-4 was the strongest stimulus for both gene expression and protein production of the chemokines RANTES, IL-8 and gro-alpha, while both IL-13 and IFN-gamma were weaker inducers of these chemokines, with the exception of gro-alpha (IL-13 was a strong stimulus for gro-alpha production). TNF-alpha synergized with IL-4, and to a lesser extent with IFN-gamma and IL-13, to release RANTES, IL-8 and gro-alpha. IL-4 and to a lesser extent IL-13 and IFN-gamma stimulated the production of MCP-3 and -4, eotaxin and eotaxin-2 immunoreactivities. However, no induction of the mRNAs encoding these chemokines was observed, suggesting that they may be released from a preformed pool within the HAECs. Conclusion: These findings suggest that when released into the airways, Th2- and to a lesser extent Th1-type cytokines may stimulate recruitment of eosinophils and neutrophils through the release of CC (RANTES, MCP-3 and -4, eotaxin and eotaxin-2) and CXC chemokines (gro-alpha and IL-8).

Muramyl dipeptide mediated activation of human bronchial epithelial cells interacting with basophils: a novel mechanism of airway inflammation

“…Our present results show that bronchial epithelial cells were the major source for the release of IL-6, CXCL8 and b-defensin2 in co-culture upon MDP stimulation. For innate immunity against microbial infection, activated bronchial epithelial cells are potent sources of a wide variety of proinflammatory cytokines and chemokines, such as CXCL8 [44,45]. Apart from MDP, Gram-negative bacterial cell wall component lipopolysaccharide and human rhinovirus can also activate epithelial cells to release anti-bacterial peptide b-defensin 2 [46,47].…”

Matrix Metalloproteinase-8 Deficiency Promotes Granulocytic Allergen-Induced Airway Inflammation

“…Interestingly, IL-4 has been reported to induce a delay of neutrophil apoptosis (36), suggesting that IL-4 by itself could play a role in the reduction of neutrophilic apoptosis observed in the lung and leading to neutrophil accumulation in the BALF. In addition, IL-4 is a multifunctional cytokine that can regulate the secretion of neutrophil-attracting chemokines such as growth-related oncogene-␣ and IL-8 (37), and control the expression of VCAM-1 on the surface of vascular endothelial cells (38), thereby modulating neutrophil recruitment and trafficking. In the present study, increased IL-4 levels are linked with anti-OVA-specific IgE levels that were strongly enhanced in the serum of MMP-8 Ϫ/Ϫ .…”

IL-12 Contributes to Allergen-Induced Airway Inflammation in Experimental Asthma

“…Similarly, Wang et al (19) identified IL-12 as a potential inducer of VCAM-1 expression. Also, IFN-␥ has been shown to induce expression of the named chemokines (31)(32)(33). One might speculate that, during the repeated airway challenges, IL-12 contributes directly or through an IFN-␥-dependent mechanism to enhanced expression of Th2 cytokines, eosinophil-recruiting chemokines, and VCAM-1.…”