Mycoplasma pneumoniae induces airway epithelial cell expression of MUC5AC in asthma

Abstract

As excess mucin expression can contribute to the exacerbation of asthma, the present authors hypothesised that Mycoplasma pneumoniae significantly induces MUC5AC (the major airway mucin) expression in airway epithelial cells isolated directly from asthmatic subjects.A total of 11 subjects with asthma and six normal controls underwent bronchoscopy with airway brushing. Epithelial cells were cultured at an air-liquid interface and incubated with and without M. pneumoniae for 48 h, and in the presence and absence of nuclear factor (NF)-kB and a toll-like receptor (TLR)2 inhibitor. Quantitative PCR was performed for MUC5AC and TLR2 mRNA. MUC5AC protein and total protein were determined by ELISA.M. pneumoniae exposure significantly increased MUC5AC mRNA and protein expression after 48 h in epithelial cells isolated from asthmatic, but not from normal control subjects, at all concentrations as compared to unexposed cells. TLR2 mRNA expression was significantly increased in asthmatic epithelial cells at 4 h compared with unexposed cells. NF-kB and TLR2 inhibition reduced MUC5AC expression to the level of the unexposed control in both groups.Mycoplasma pneumoniae exposure significantly increased MUC5AC mRNA and protein expression preferentially in airway epithelial cells isolated from asthmatic subjects. The toll-like receptor 2 pathway may be involved in this process.

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers

“…In support of the hypothesis that asthmatic airways are more susceptible to M. pneumoniae infection, Toll-like receptor 2 expression and interleukin (IL)-6 production are downregulated by M. pneumoniae infection during ongoing ovalbumin-induced allergic inflammation [57]. Moreover, airway epithelial cells from asthmatic subjects show increased production of mucin 5 subtypes A and C (the major airway mucin) when infected with M. pneumoniae compared to normal controls [58]. These data suggest that pre-existing inflammation might lead to decreased clearance of M. pneumoniae, thus increasing airway inflammation.…”

Contamination of Tissue Cultures by Mycoplasmas

“…Hyperammonia toxicity in irradiated hepatoma cells has been shown to be due to contamination by mycoplasma containing arginine deiminase, that converts arginine to citrulline and ammonia [54]. M. pneumoniae induces the expression of the major airway protein mucin (MUC5AC) in cultured airway epithelial cells isolated from asthmatic subjects, but not in cells isolated from normal subjects; the preferential expression of MUC5AC in cells isolated from asthmatic subjects suggests that asthmatic epithelial cells may be primed to respond to the mycoplasma [81], thus pointing to the importance of identifying consequences of mycoplasma contamination that may be observed only in certain specific types of cultured cells. Catabolic mycoplasmal enzymes may interfere with chemotherapy.…”

“…Mycoplasmas and mycoplasmal LPP are known to activate the transcription factors NF-B [74,79] and AP-1 [1 4], via TLRdownstream cascades involving kinases (MAPKKKs-IKKs and MAPKKKs-MAPKKsMAPKs). Known mycoplasma-affected target genes are mainly those responsible for proinflammatory proteins [4], and those involved in malignant cell transformation [72], with little information available on genes responsible for other proteins [53,79,80,81].…”

Toll-Like Receptor 2 andMuc2Expression on Human Intestinal Epithelial Cells by Gymnophalloides seoi Adult Antigen

“…In rat biliary epithelia, treatment with anti-TLR2 antibodies or anti-TLR4 antibodies downregulated MUC2 expression that had been induced by lipopolysaccharide (LPS) (Ikeda et al, 2007). Kraft et al (2008) suggested that the TLR2 signaling pathway is involved in MUC5AC expression in airway epithelial cells exposed to Mycoplasma pneumoniae.…”

“…The membranetethered mucins, MUC1, MUC3, MUC4, MUC12, and MUC13, may contribute to airway mucus obstruction (Rose et al, 2001). Most mucin studies have focused on the respiratory epithelial layer in asthma models (Cohn et al, 1999;Kraft et al, 2008). However, intestinal parasitic infections also trigger mucin hypersecretion, which is an important response of the innate immune system (Moncada et al, 2003).…”