Microarray analysis of Streptococcus pneumoniae gene expression changes to human lung epithelial cells

2008 ◽  
Vol 54 (3) ◽  
pp. 189-200 ◽  
Author(s):  
Xin-Ming Song ◽  
Wayne Connor ◽  
Shakiba Jalal ◽  
Karsten Hokamp ◽  
Andrew A. Potter

Streptococcus pneumoniae infection starts from the respiratory tract where interaction with host epithelial cells occurs. To gain more insights on pneumococcal pathogenesis, an oligonucleotide (oligo)-based microarray was used to investigate gene expression changes of one serotype 3 encapsulated pathogenic S. pneumoniae strain 82 and one unencapsulated avirulent S. pneumoniae strain R6 upon exposure to human lung epithelial cells (A549) for 1 and 3 h, respectively. We observed that genes associated with many functional categories were differentially regulated in strain 82, such as genes in pathogenesis, cell envelope, transcription, translation, transport, metabolism, and unknown functions. In contrast, few genes were changed in strain R6 except for genes in ribonucleotide biosynthesis and unknown functions. Quantitative real-time PCR analysis confirmed the microarray results for most of the genes tested. To further characterize functions of the selected genes, knockout mutants were constructed in strain R6. We demonstrated that 2 genetic loci, SP_2170 (AdcB, zinc ABC transporter) and SP_0157 (hypothetical protein), were involved in adherence to A549 cells. These data suggest that divergent gene expression changes occur in S. pneumoniae pathogenic and avirulent strains during interaction with human lung epithelial cells. Some of those genes are involved in pneumococcal pathogenesis.

2001 ◽  
Vol 280 (1) ◽  
pp. L30-L38 ◽  
Author(s):  
Jun Araya ◽  
Muneharu Maruyama ◽  
Kazuhiko Sassa ◽  
Tadashi Fujita ◽  
Ryuji Hayashi ◽  
...  

Radiation pneumonitis is a major complication of radiation therapy. However, the detailed cellular mechanisms have not been clearly defined. Based on the recognition that basement membrane disruption occurs in acute lung injury and that matrix metalloproteinase (MMP)-2 can degrade type IV collagen, one of the major components of the basement membrane, we hypothesized that ionizing radiation would modulate MMP-2 production in human lung epithelial cells. To evaluate this, the modulation of MMP-2 with irradiation was investigated in normal human bronchial epithelial cells as well as in A549 cells. We measured the activity of MMP-2 in the conditioned medium with zymography and the MMP-2 mRNA level with RT-PCR. Both of these cells constitutively expressed 72-kDa gelatinolytic activity, corresponding to MMP-2, and exposure to radiation increased this activity. Consistent with the data of zymography, ionizing radiation increased the level of MMP-2 mRNA. This radiation-induced increase in MMP-2 expression was mediated via p53 because the p53 antisense oligonucleotide abolished the increase in MMP-2 activity as well as the accumulation of p53 after irradiation in A549 cells. These results indicate that MMP-2 expression by human lung epithelial cells is involved in radiation-induced lung injury.


2008 ◽  
Vol 1 (1) ◽  
pp. 64 ◽  
Author(s):  
Xin-Ming Song ◽  
Wayne Connor ◽  
Karsten Hokamp ◽  
Lorne A Babiuk ◽  
Andrew A Potter

2004 ◽  
Vol 78 (15) ◽  
pp. 8146-8158 ◽  
Author(s):  
Santanu Bose ◽  
Mausumi Basu ◽  
Amiya K. Banerjee

ABSTRACT Human parainfluenza virus type 3 (HPIV-3) is an airborne pathogen that infects human lung epithelial cells from the apical (luminal) plasma membrane domain. In the present study, we have identified cell surface-expressed nucleolin as a cellular cofactor required for the efficient cellular entry of HPIV-3 into human lung epithelial A549 cells. Nucleolin was enriched on the apical cell surface domain of A549 cells, and HPIV-3 interacted with nucleolin during entry. The importance of nucleolin during HPIV-3 replication was borne out by the observation that HPIV-3 replication was significantly inhibited following (i) pretreatment of cells with antinucleolin antibodies and (ii) preincubation of HPIV-3 with purified nucleolin prior to its addition to the cells. Moreover, HPIV-3 cellular internalization and attachment assays performed in the presence of antinucleolin antibodies and purified nucleolin revealed the requirement of nucleolin during HPIV-3 internalization but not during attachment. Thus, these results suggest that nucleolin expressed on the surfaces of human lung epithelial A549 cells plays an important role during HPIV-3 cellular entry.


2013 ◽  
Vol 62 (8) ◽  
pp. 1144-1152 ◽  
Author(s):  
Sara Remuzgo-Martínez ◽  
Lilian Pilares-Ortega ◽  
Lorena Álvarez-Rodríguez ◽  
Maitane Aranzamendi-Zaldunbide ◽  
Daniel Padilla ◽  
...  

Rhodococcus equi is an opportunistic human pathogen associated with immunosuppressed people. While the interaction of R. equi with macrophages has been comprehensively studied, little is known about its interactions with non-phagocytic cells. Here, we characterized the entry process of this bacterium into human lung epithelial cells. The invasion is inhibited by nocodazole and wortmannin, suggesting that the phosphatidylinositol 3-kinase pathway and microtubule cytoskeleton are important for invasion. Pre-incubation of R. equi with a rabbit anti-R. equi polyclonal antiserum resulted in a dramatic reduction in invasion. Also, the invasion process as studied by immunofluorescence and scanning electron microscopy indicates that R. equi make initial contact with the microvilli of the A549 cells, and at the structural level, the entry process was observed to occur via a zipper-like mechanism. Infected lung epithelial cells upregulate the expression of cytokines IL-8 and IL-6 upon infection. The production of these pro-inflammatory cytokines was significantly enhanced in culture supernatants from cells infected with non-mucoid plasmid-less strains when compared with cells infected with mucoid strains. These results demonstrate that human airway epithelial cells produce pro-inflammatory mediators against R. equi isolates.


2021 ◽  
Vol 7 ◽  
Author(s):  
Prabhash Kumar Jha ◽  
Aatira Vijay ◽  
Arda Halu ◽  
Shizuka Uchida ◽  
Masanori Aikawa

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative virus for the current global pandemic known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 belongs to the family of single-stranded RNA viruses known as coronaviruses, including the MERS-CoV and SARS-CoV that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), respectively. These coronaviruses are associated in the way that they cause mild to severe upper respiratory tract illness. This study has used an unbiased analysis of publicly available gene expression datasets from Gene Expression Omnibus to understand the shared and unique transcriptional signatures of human lung epithelial cells infected with SARS-CoV-2 relative to MERS-CoV or SARS-CoV. A major goal was to discover unique cellular responses to SARS-CoV-2 among these three coronaviruses. Analyzing differentially expressed genes (DEGs) shared by the three datasets led to a set of 17 genes, suggesting the lower expression of genes related to acute inflammatory response (TNF, IL32, IL1A, CXCL1, and CXCL3) in SARS-CoV-2. This subdued transcriptional response to SARS-CoV-2 may cause prolonged viral replication, leading to severe lung damage. Downstream analysis of unique DEGs of SARS-CoV-2 infection revealed changes in genes related to apoptosis (NRP1, FOXO1, TP53INP1, CSF2, and NLRP1), coagulation (F3, PROS1, ITGB3, and TFPI2), and vascular function (VAV3, TYMP, TCF4, and NR2F2), which may contribute to more systemic cardiovascular complications of COVID-19 than MERS and SARS. The study has uncovered a novel set of transcriptomic signatures unique to SARS-CoV-2 infection and shared by three coronaviruses, which may guide the initial efforts in the development of prognostic or therapeutic tools for COVID-19.


2012 ◽  
Vol 9 (1) ◽  
pp. 6 ◽  
Author(s):  
Timothy N Perkins ◽  
Arti Shukla ◽  
Paul M Peeters ◽  
Jeremy L Steinbacher ◽  
Christopher C Landry ◽  
...  

2012 ◽  
Vol 130 (1) ◽  
pp. 145-157 ◽  
Author(s):  
Rasmus Foldbjerg ◽  
Eveline S. Irving ◽  
Yuya Hayashi ◽  
Duncan S. Sutherland ◽  
Kasper Thorsen ◽  
...  

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