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A network-based ana...
A network-based analysis of the late-phase reaction of the skin.
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- Benson, Mikael, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences,Department of Pediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden
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- Adner, Mikael (author)
- Karolinska Institutet,Lund University,Lunds universitet,Klinisk och experimentell allergiforskning,Laryngoesofagologi, allergi och livskvalitet,Forskargrupper vid Lunds universitet,Clinical and Experimental Allergy Research,Laryngoesophagology, Allergy and Life Quality,Lund University Research Groups,Department of Computer Science, University of Tennessee, Knoxville, USA,Laboratory for Clinical and Experimental Allergy Research, Department of Oto-Rhino-Laryngology, Malmö University Hospital, Lund University, Malmö, Sweden
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Adner, Mikael (author)
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- Andersson, Bengt A., 1952 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology,Department of Clinical Immunology, Sahlgrenska Academy, Gothenburg, Sweden
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- Torinsson Naluai, Åsa, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,Department of Clinical Genetics and Göteborg Genomics, Sahlgrenska Academy, Gothenburg, Sweden
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- Cardell, Lars-Olaf (author)
- Lund University,Lunds universitet,Klinisk och experimentell allergiforskning,Laryngoesofagologi, allergi och livskvalitet,Forskargrupper vid Lunds universitet,Clinical and Experimental Allergy Research,Laryngoesophagology, Allergy and Life Quality,Lund University Research Groups,Laboratory for Clinical and Experimental Allergy Research, Department of Oto-Rhino-Laryngology, Malmö University Hospital, Lund University, Malmö, Sweden
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(creator_code:org_t)
- Elsevier BV, 2006
- 2006
- English.
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In: The Journal of allergy and clinical immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 118:1, s. 220-5
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Abstract
Subject headings
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- BACKGROUND: The late-phase reaction (LPR) of the skin is an in vivo model of allergic inflammation. OBJECTIVE: We sought to identify disease-associated pathways in the LPR using a network-based analysis. METHODS: The LPR was examined by means of DNA microarray analysis of skin biopsy specimens from 10 patients with allergic rhinitis and 10 healthy control subjects. The results were further analyzed in 2 different materials consisting of nasal fluids and allergen-challenged CD4(+) T cells from patients with allergic rhinitis. RESULTS: The DNA microarray analysis revealed several genes of known relevance to allergy. The eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes Charcot-Leyden crystal protein differed most in expression. A network-based analysis showed upregulation of IL-4- and CCL4-dependent pathways and downregulation of a TGF-beta-induced pathway. CCL4 is expressed by CD4(+) T cells and chemotactic for eosinophils. We hypothesized that allergen induces release of CCL4 from T(H)2 cells and that this contributes to influx of eosinophils. Further analysis showed increase of CCL4 protein in nasal fluids from allergic patients during the season. Allergen challenge of PBMCs resulted in proliferation of T(H)2 cells and increased production of CCL4 in CD4(+) T cells from allergic patients. An analysis of the DNA microarray data revealed a significant correlation between CCL4 and the eosinophil marker CLC. CONCLUSION: A network-based analysis of the LPR showed increased activity of IL-4- and CCL4- dependent pathways and downregulation of the TGF-beta-induced pathway. Allergen-induced release of CCL4 from T(H)2 cells might contribute to influx of eosinophils during the LPR. CLINICAL IMPLICATIONS: Involvement of multiple interacting pathways indicates that it might be difficult to identify one single mediator as a biomarker or drug target in allergic inflammation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- Adult
- CD4-Positive T-Lymphocytes
- immunology
- Chemokines
- CC
- physiology
- Humans
- Interleukin-4
- physiology
- Macrophage Inflammatory Protein-1
- physiology
- Middle Aged
- Oligonucleotide Array Sequence Analysis
- Rhinitis
- Allergic
- Perennial
- immunology
- Rhinitis
- Allergic
- Seasonal
- immunology
- Signal Transduction
- Skin
- immunology
- Transforming Growth Factor beta
- physiology
- late-phase reaction
- DNA microarrays
- gene expression
- DNA microarrays; gene expression; late-phase reaction
Publication and Content Type
- ref (subject category)
- art (subject category)
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