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 T(H)2 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 T(H)2 cytokine transcription suggests that increased 90K protein expression is an attempt to limit the ongoing inflammation in asthma.