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.
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.


CONCLUSIONS
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).
Meyer-Hoffert
Ulf
U
Department of Dermatology, University of Kiel, Kiel, Germany. umeyerhoffert@dermatology.uni-kiel.de
Lezcano-Meza
Diana
D
Bartels
Joachim
J
Montes-Vizuet
Aurea Rosalia
AR
Schröder
Jens-M
JM
Teran
Luis M
LM
D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D054410:Chemokine CCL7; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
C515456:CCL11 protein, human; C099677:CCL13 protein, human; C515450:CCL7 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D016209:Interleukin-8; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger