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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 29, 2012 |
| Title |
Transcript analysis in response to ozone in mice deficient in TLR4 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
We previously identified toll-like receptor 4 (Tlr4) as a candidate gene responsible for ozone (O3)-induced pulmonary hyperpermeability and inflammation. The objective of this study was to determine the mechanism through which TLR4 modulates O3-induced pulmonary responses and to utilize transcriptomics to determine TLR4 effector molecules. C3H/HeJ (HeJ; Tlr4 mutant) and C3H/HeOuJ (OuJ; Tlr4 normal), mice were exposed continuously to 0.3 ppm O3 or filtered air for 6, 24, 48 or 72 hr. Affymetrix Mouse430A_MOE gene arrays were used to analyze lung homogenates from HeJ and OuJ mice followed using a bioinformatic analysis. Inflammation was assessed by bronchoalveolar lavage and molecular analysis by ELISA, immunoblotting, and transcription factor activity. TLR4 signals through both the MYD88-dependent and independent pathways in OuJ mice, which involves MAP kinase activation, NF-kappaB, AP-1, and KC. Microarray analyses identifiedTLR4 responsive genes for strain and time in OuJ versus HeJ mice (p<0.05). One significantly upregulated cluster of genes in OuJ were the heat shock proteins (Hspa1b; Hsp70), Hsp90ab1). Furthermore, O3-induced expression of HSP70 protein was increased in OuJ compared to HeJ mice following 24-48 h O3. Moreover, BAL polymorphonuclear leukocytes (PMN) and total protein were significantly reduced in response to O3 in Hspa1a/Hspa1btm1Dix (Hsp70-/-) compared to Hsp70+/+ mice (p<0.05). TLR4 signaling (MYD88-dependent), ERK1/2, AP-1 activity, and KC protein content were also significantly reduced after O3 exposure in Hsp70-/- compared to Hsp70+/+ mice (p<0.05). These studies suggest that HSP70 is involved in the regulation of O3-induced lung inflammation through the TLR4 pathway and provide evidence that HSP70 is an endogenous in vivo TLR4 ligand.
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| Overall design |
Two strains of mice were used for these studies. The C3H/HeJ with a dominant negative Tlr4 and the C3H/HeOuJ mice with a sufficient Tlr4. Total RNA was extracted from left lung lobes (air, 6, 24, 48 hr of O3 exposure for OuJ and HeJ mice; n = 3 per treatment group). Therefore a total of 24 arrays with 3 different ozone exposure times and 1 air exposure.
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| Contributor(s) |
Bauer AK, Rondini EA, Hummel K, Degraff LM, Walker C, Jedlicka AE, Kleeberger SR |
| Citation(s) |
21543283, 34573120 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| K22 ES014731 |
The role of toll-like receptor 4 in O3-induced lung inflammation and injury. |
MICHIGAN STATE UNIVERSITY |
ALISON K BAUER |
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| Submission date |
Mar 09, 2010 |
| Last update date |
Oct 06, 2021 |
| Contact name |
Alison Kendall Bauer |
| E-mail(s) |
alison.bauer@ucdenver.edu
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| Organization name |
University of Colorado Denver
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| Department |
Environmental and Occupational Health
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| Street address |
12850 E. Montview Blvd.; Rm 3125
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| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (1) |
| GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
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| Samples (24)
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| GSM519979 |
OuJ, 6 hr Ozone, biological rep 1 |
| GSM519980 |
OuJ, 6 hr Ozone, biological rep 2 |
| GSM519981 |
OuJ, 6 hr Ozone, biological rep 3 |
| GSM519982 |
OuJ, 24 hr Ozone, biological rep 1 |
| GSM519983 |
OuJ, 24 hr Ozone, biological rep 2 |
| GSM519984 |
OuJ, 24 hr Ozone, biological rep 3 |
| GSM519985 |
OuJ, 48 hr Ozone, biological rep 1 |
| GSM519986 |
OuJ, 48 hr Ozone, biological rep 2 |
| GSM519987 |
OuJ, 48 hr Ozone, biological rep 3 |
| GSM519988 |
HeJ, air, biological rep 1 |
| GSM519989 |
HeJ, air, biological rep 2 |
| GSM519990 |
HeJ, air, biological rep 3 |
| GSM519991 |
HeJ, 6 hr Ozone, biological rep 1 |
| GSM519992 |
HeJ, 6 hr Ozone, biological rep 2 |
| GSM519993 |
HeJ, 6 hr Ozone, biological rep 3 |
| GSM519994 |
HeJ, 24 hr Ozone, biological rep 1 |
| GSM519995 |
HeJ, 24 hr Ozone, biological rep 2 |
| GSM519996 |
HeJ, 24 hr Ozone, biological rep 3 |
| GSM519997 |
HeJ, 48 hr Ozone, biological rep 1 |
| GSM519998 |
HeJ, 48 hr Ozone, biological rep 2 |
| GSM519999 |
HeJ, 48 hr Ozone, biological rep 3 |
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| Relations |
| BioProject |
PRJNA124909 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE20715_RAW.tar |
50.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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