Role of 90K protein in asthma and TH2-type cytokine expression.
BACKGROUND
The 90K protein (mac-2 binding protein) is a member of the macrophage scavenger receptor cysteine-rich domain superfamily. Although systemic levels of 90K protein have been correlated with inflammation in many diseases, its role in asthma is unknown.


OBJECTIVE
To determine whether asthma is associated with changes in the local and systemic expression of 90K protein and whether 90K protein affects the TH2 cytokine profile that is a hallmark of asthma.


METHODS
The 90K protein levels were measured in the systemic circulation of 69 individuals with asthma and 68 controls and in the bronchoalveolar lavage fluid of 9 controls and 7 atopic asthmatic patients before and after segmental allergen challenge. The effects of 90K protein on interleukin 4 (IL-4), IL-5, IL-13, and IL-6 production at protein and transcriptional levels in cultured human peripheral blood mononuclear cells were determined.


RESULTS
Plasma concentrations of 90K protein were higher in asthmatic individuals vs controls (P = .002), were higher in the bronchoalveolar lavage fluid of asthmatic patients vs controls (P < .01), and increased after segmental allergen challenge in atopic asthmatic patients (P < .03). Increasing concentrations of 90K protein resulted in significantly reduced IL-4, IL-5, and IL-13 concentrations and increased IL-6 concentrations in the supernatants of cultured peripheral blood mononuclear cells (P < .05). Reverse transcriptase-polymerase chain reaction studies showed parallel changes in the transcription of these cytokines.


CONCLUSIONS
Local and systemic concentrations of 90K protein are increased in asthma. Its inhibitory effect on TH2 cytokine transcription suggests that increased 90K protein expression is an attempt to limit the ongoing inflammation in asthma.
Kalayci
Omer
O
The Combined Program in Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Birben
Esra
E
Tinari
Nicola
N
Oguma
Tsuyoshi
T
Iacobelli
Stefano
S
Lilly
Craig M
CM
D000328:Adult; D000951:Antigens, Neoplasm; D001249:Asthma / Q000276:immunology*; D014408:Biomarkers, Tumor; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002352:Carrier Proteins; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004804:Eosinophils / Q000502:physiology; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D006023:Glycoproteins; D006801:Humans; D008074:Lipoproteins / Q000032:analysis / Q000502:physiology*; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D018418:Th2 Cells / Q000276:immunology*; D016326:Extracellular Matrix Proteins
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D016207:Cytokines; D037502:Galectin 3; D006023:Glycoproteins; D008074:Lipoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins