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

Int Arch Allergy Immunol. 2003 Aug;131(4):264-71. doi: 10.1159/000072138.


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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CCL11
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / immunology
  • Chemokine CCL7
  • Chemokines, CC / biosynthesis*
  • Chemokines, CC / genetics
  • Chemokines, CC / immunology
  • Chemokines, CXC / biosynthesis*
  • Chemokines, CXC / genetics
  • Chemokines, CXC / immunology
  • Cytokines / immunology
  • Cytokines / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Humans
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Monocyte Chemoattractant Proteins / biosynthesis
  • Monocyte Chemoattractant Proteins / genetics
  • Monocyte Chemoattractant Proteins / immunology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Up-Regulation


  • CCL11 protein, human
  • CCL13 protein, human
  • CCL7 protein, human
  • Chemokine CCL11
  • Chemokine CCL5
  • Chemokine CCL7
  • Chemokines, CC
  • Chemokines, CXC
  • Cytokines
  • Interleukin-8
  • Monocyte Chemoattractant Proteins
  • RNA, Messenger