Early distinction between severe Mycoplasma pneumoniae pneumonia (MPP) and mild MPP is still difficult. The aim of this study was to analyze cytokines in bronchoalveolar lavage fluid (BALF) and explore predicting factors of severe MPP in children. Retrospective analysis was performed on 150 children with MPP or bronchial foreign body (FB) admitted in our hospital. The mRNA levels of IL17A were found significantly lower in severe MPP group comparing with mild MPP group or FB group. However, no significant difference was found in the levels of IL4, IL10 or interferon beta1 (IFNβ1) between the two groups. Receiver operator characteristic (ROC) curve analysis showed that IL17A can be used to distinguish severe MPP from mild MPP. These results were confirmed in a validation cohort including 40 MPP children from another hospital. IL17A levels were correlated with some clinical characters, such as refractoriness and pleural effusion. Lower IL17A levels were more likely to be found in refractory MPP children or in MPP children with pleural effusion. Moreover, the protein levels of IL17A in BALF were also found greatly decreased in children with severe MPP. Thus, decreased IL17A levels in BALF may be a valuable biomarker to identify severe MPP in children.

Gene amplifications in the 17q chromosomal region are observed frequently in breast cancers. An integrative bioinformatics analysis of this region nominated the MAP3K 3 gene as a potential therapeutic target in breast cancer. This gene encodes mitogen-activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), which has not yet been reported to be associated with cancer-causing genetic aberrations. We found that MAP3K3 was amplified in approximately 8–20% of breast cancers. Knockdown of MAP3K3 expression significantly inhibited cell proliferation and colony formation in MAP3K3-amplified breast cancer cell lines MCF-7 and MDA-MB-361 but not in MAP3K3 non-amplified breast cancer cells. Knockdown of MAP3K3 expression in MAP3K3-amplified breast cancer cells sensitized breast cancer cells to apoptotic induction by TNFα and TRAIL, as well as doxorubicin, VP-16 and fluorouracil, three commonly used chemotherapeutic drugs for treating breast cancer. In addition, ectopic expression of MAP3K3, in collaboration with Ras, induced colony formation in both primary mouse embryonic fibroblasts and immortalized human breast epithelial cells (MCF-10A). Combined, these results suggest that MAP3K3 contributes to breast carcinogenesis and may endow resistance of breast cancer cells to cytotoxic chemotherapy. Therefore, MAP3K3 may be a valuable therapeutic target in patients with MAP3K3-amplified breast cancers, and blocking MAP3K3 kinase activity with a small molecule inhibitor may sensitize MAP3K3-amplified breast cancer cells to chemotherapy.

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Host immune response may be involved in the pathogenesis of children Mycoplasma pneumoniae pneumonia (MPP). In the current study, we investigated the alterations of cytokines levels among control, mild MPP and severe MPP children to determine whether cytokine signatures associate with MPP and correlate with disease severity. We measured 13 cytokines in bronchoalveolar lavage fluid (BALF) of 88 children with MPP and 26 children with foreign body aspiration (FB) using a Luminex system. Linear discriminant analyses were performed to develop predictive models of mild MPP and severe MPP on these children. We observed nearly complete separations of severe MPP group, mild MPP group and control group in linear discriminant analyses. Eleven cytokines significantly increased in children with MPP, and seven cytokines had statistically significant upward linear trends correlated with MPP severity. In addition, compared to control group, both IFNγ/IL4 ratio and IFNγ/IL13 ratio increased in mild MPP and severe MPP groups. Our results suggest that children MPP can alter BALF cytokines signatures which associate with disease severity and can be characterized by a distinct airway molecular phenotype that has elevated Th1/Th2 ratios.