RESULTS The levels of serum IgE and IgG in BLA- or Dex- treated mice were significantly reduced compared to those in the asthma (AS) group (P<0.01), whereas the levels of cytokines IL-4, TNF-α, and MCP-1 were significantly decreased (P<0.01).
Higher relative abundance of these bacteria is furthermore associated with an airway immune profile dominated by reduced TNF-α and IL-1β and increased CCL2 and CCL17, which itself is an independent predictor for asthma.
This study was aimed to determine the profiles of serum cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP-1: monocyte chemoattract protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non-asthmatic background with bacterial, viral or mixed acute respiratory infection.
Air-liquid interface cultures of human bronchial epithelial cells (HBEC) of control subjects (cHBEC) or severe asthma patients (saHBEC) were co-cultured with monocyte-derived dendritic cells (moDC).Increased release of CXCL8, TSLP and IL-33 from saHBEC contrasted with cHBEC producing CXCL10 and CCL2.
We demonstrated that CCL2 and IL-17 levels and the frequency of Th17 and Tc17 cells in lung tissues and bronchoalveolar lavage fluid increased in the asthma group compared with the normal control mice.
Finally, bronchoalveolar macrophages from children with asthma elaborated more CCL2 upon ex vivo exposure to HRV than cells from nonasthmatic patients.
No association was observed between the four polymorphisms and the presence of atopic rhinitis or atopic conjunctivitis and an elevated rate of serum IgE over 200 IU/ml.Additional effects of MCP-1 and its receptor CCR2 polymorphisms seem to be involved in disease susceptibility to asthma in Tunisian patients; nevertheless they could be protective against its severe forms.
In addition, we generated conditional knockout mice in which Abl expression in smooth muscle was disrupted, and then evaluated the effects of Abl conditional knockout on airway resistance, smooth muscle mass, cell proliferation, IL-13 and CCL2 in the mouse model of asthma.
In asthma patients, the consistently elevated serum levels of MCP-1 suggest its role in the pathogenesis of bronchial asthma - not only in the chronic inflammatory processes, but also in acute asthma attack exacerbation.
The finding in the family study that the CCL2-2578G allele was transmitted less often by heterozygous parents to their children with asthma (P=0.0016) confirms the association of CCL2-2578G with asthma risk.
Furthermore, this polymorphism seems to play no role in the development of asthma or atopy in Chinese subjects, possibly as a result of the genetic heterogeneity between Asian and Caucasian populations with respect to regulation of MCP-1 expression.
We conclude that cells contained in the bronchial secretions from asthmatics express higher amounts of mRNA for MMP-1 and TIMP-1, perhaps related to an increased expression of MCP-1, which might contribute to the extracellular matrix changes observed during airway remodelling.
In this cohort of children, there are associations between carrying G at -2518 of the MCP-1 gene regulatory region and the presence of asthma as well as between asthma severity and homozygosity for the G allele.