Acute high-level exposure to WTC particles alters expression of genes associated with oxidative stress and immune function in the lung

Figures & data

Figure 1. Venn diagram illustrating number of genes significantly changed by isoflurane (ISO) alone (vs naïve) and by WTC dust exposure (under ISO anesthesia) in rat lungs. ISO by itself changed 1151 genes; when dust was combined with ISO, 1000 genes were changed – of which 232 were in common with ISO, but 166 were due to WTC dust exposure.

Table 1. Top 30 genes induced in lungs by WTC dust relative to by isoflurane (ISO) only.

Gene symbol	Gene title	Entry gene ID	ISO/Naïve	WTC/Naïve	WTC/ISO
CXCL2	chemokine (C-X-C motif) ligand 2	114105	1.18	12.23	10.38
CCL20	chemokine (C-C motif) ligand 20	29538	−1.02	10.01	10.17
CYP1A1	cytochrome P450, family 1, subfamily a	24296	−1.04	9.07	9.43
CXCL1	chemokine (C-X-C motif) ligand 1	81503	2.07	16.24	7.83
LCN2	lipocalin 2	170496	1.98	13.32	6.73
MT1A	metallothionein 1a	24567	1.44	9.34	6.50
TMPRSS8	transmembrane protease, serine 8 (intestinal)	287106	1.02	6.51	6.40
CCL7	chemokine (C-C motif) ligand 7	287561	−1.28	4.80	6.13
PTGS2	prostaglandin-endoperoxide synthase 2	29527	1.08	6.61	6.12
ACTA1	actin, α1, skeletal muscle	29437	1.28	6.96	5.43
IL1R2	IL-1 receptor, type II	117022	1.17	5.84	4.99
S100A8	S100 calcium binding protein A8	116547	−1.88	2.52	4.73
CCL2	chemokine (C-C motif) ligand 2	24770	−1.02	4.61	4.72
TFPI2	tissue factor pathway inhibitor 2	286926	−1.10	4.20	4.63
ALDH3A1	aldehyde dehydrogenase 3 family, member A1	25375	1.01	4.63	4.57
SELP	selectin P	25651	−1.21	3.64	4.40
RND1	Rho family GTPase 1	362993	1.03	4.34	4.23
CALCB	calcitonin-related polypeptide, beta	171519	−1.03	4.08	4.22
NOS2	nitric oxide synthase 2, inducible	24599	−1.56	2.55	3.99
IL1B	IL-1 beta	24494	−1.99	2.00	3.98
PGLYRP1	peptidoglycan recognition protein 1	84387	−1.44	2.58	3.70
IL6	IL-6	24498	1.08	3.96	3.65
EGR1	early growth response 1	24330	−1.54	2.32	3.58
TIMP1	TIMP metallopeptidase inhibitor 1	116510	1.03	3.63	3.53
CX3CL1	chemokine (C-X3-C motif) ligand 1	89808	1.06	3.63	3.42
CXCL10	chemokine (C-X-C motif) ligand 10	245920	−1.17	2.76	3.24
SOD2	superoxide dismutase 2, mitochondrial	24787	1.09	3.45	3.16
HAMP	hepcidin antimicrobial peptide	84604	1.11	3.45	3.11
JUNB	jun B proto-oncogene	24517	−1.04	2.92	3.04
NFIL3	nuclear factor, IL-3-regulated	114519	−1.02	2.94	2.99

Some gene names were truncated to fit in the table. Genes without annotation were removed from the list. Note that many genes induced in the lungs of WTC dust-exposed rats generally were down-regulated in ISO only-exposed rats, suggesting likely opposing effects of ISO and WTC dust.

Table 2. Top 30 genes inhibited in lungs by WTC dust relative to by isoflurane (ISO) only.

Gene symbol	Gene title	Entry gene ID	ISO/Naïve	WTC/Naïve	WTC/ISO
FGFBP1	fibroblast growth factor binding protein 1	64535	1.03	−3.02	−3.12
POLA2	polymerase (DNA directed), α2	85242	−1.08	−2.83	−2.62
MX2	myxovirus (influenza virus) resistance 2	286918	1.31	−1.93	−2.53
METTL7A	methyltransferase like 7A	315306	2.97	1.32	−2.25
CDC42EP1	CDC42 effector protein (Rho GTPase binding) 1	315121	3.22	1.45	−2.22
MAPK3	mitogen activated protein kinase 3	50689	2.98	1.35	−2.21
TAGLN2	transgelin 2	304983	4.09	1.93	−2.12
MX1	myxovirus (influenza virus) resistance 1	24575	−1.04	−2.19	−2.11
RPL13A	ribosomal protein L13A	317646	2.30	1.11	−2.07
CAP1	CAP, adenylate cyclase-associated protein 1 (yeast)	64185	4.16	2.07	−2.01
LY6C	Ly6-C antigen	56778	1.54	−1.30	−2.00
SLC7A10	solute carrier family 7 (neutral amino acid transporter)	114518	1.22	−1.64	−2.00
EEF1A1	eukaryotic translation elongation factor 1 α1	1E + 08	6.31	3.21	−1.96
TPPP3	tubulin polymerization-promoting protein, member 3	291966	1.23	−1.59	−1.95
GPX1	glutathione peroxidase 1	24404	1.57	−1.23	−1.92
NAAA	N-acylethanolamine acid amidase	497009	1.82	−1.05	−1.92
NFE2L1	nuclear factor, erythroid derived 2,-like 1	360610	2.45	1.29	−1.91
MEGF6	multiple EGF-like-domains 6	65049	2.15	1.14	−1.88
EIF5A	eukaryotic translation initiation factor 5A	287444	3.53	1.88	−1.88
PYGB	phosphorylase, glycogen; brain	25739	1.23	−1.51	−1.86
NDUFB8	NADH dehydrogenase (ubiquinone) 1 beta	293991	1.69	−1.10	−1.86
PPP1CA	protein phosphatase 1, catalytic subunit, α	24668	1.63	−1.14	−1.86
MGST3	microsomal glutathione S-transferase 3	289197	1.75	−1.06	−1.85
NR1D1	nuclear receptor subfamily 1, group D, member 1	252917	−1.18	−2.18	−1.84
TAP1	Transporter 1, ATP-binding cassette, sub-family B	24811	1.49	−1.23	−1.83
RT1-DB1	RT1 class II, locus Db1	294270	1.93	1.05	−1.83
FHL1	four and a half LIM domains 1	25177	1.72	−1.06	−1.83
IDH2	isocitrate dehydrogenase 2 (NADP+), mitochondrial	361596	1.61	−1.13	−1.83
EXT2	exostoses (multiple) 2	311215	1.46	−1.25	−1.82
PBXIP1	pre-B-cell leukemia homeobox interacting protein 1	310644	1.94	1.07	−1.82

Some gene names were truncated to fit in the table. Genes without annotation were removed from the list. Note that many genes inhibited in the lungs of WTC dust-exposed rats generally were induced in ISO only-exposed rats, suggesting likely opposing effects of ISO and WTC dust.

Table 3. Top 30 genes induced by isoflurane (ISO) only in lungs of rats (relative to in naïve rats).

Gene symbol	Gene title	Entry gene ID	ISO/Naïve	WTC/Naïve	WTC/ISO
EEF1A1	eukaryotic translation elongation factor 1 α1	100360150	6.31	3.21	−1.96
CAP1	CAP, adenylate cyclase-associated protein 1 (yeast)	64185	4.16	2.07	−2.01
TAGLN2	transgelin 2	304983	4.09	1.93	−2.12
SFTPD	surfactant protein D	25350	3.70	2.13	−1.74
TPM4	tropomyosin 4	24852	3.66	2.44	−1.50
MCAM	melanoma cell adhesion molecule	78967	3.64	2.47	−1.47
CAV1	caveolin 1, caveolae protein	25404	3.63	2.73	−1.33
EIF5A	eukaryotic translation initiation factor 5A	287444	3.53	1.88	−1.88
MSN	moesin	81521	3.35	2.12	−1.58
CDC42EP1	CDC42 effector protein (Rho GTPase binding) 1	315121	3.22	1.45	−2.22
MAPK3	mitogen activated protein kinase 3	50689	2.98	1.35	−2.21
METTL7A	methyltransferase like 7A	315306	2.97	1.32	−2.25
FKBP5	FK506 binding protein 5	361810	2.89	5.02	1.74
TSPAN4	tetraspanin 4	293627	2.81	1.61	−1.75
GDI1	GDP dissociation inhibitor 1	25183	2.79	1.69	−1.65
KLF9	Kruppel-like factor 9	117560	2.73	2.36	−1.15
ACTB	actin, beta	81822	2.61	1.79	−1.46
NPM1	nucleophosmin (nucleolar phosphoprotein B23, numatrin)	25498	2.60	2.02	−1.29
CTNNB1	catenin (cadherin associated protein), beta 1	84353	2.59	1.69	−1.53
CAPNS1	calpain, small subunit 1	29156	2.55	1.45	−1.76
MRC1	mannose receptor, C type 1	291327	2.46	1.62	−1.52
ACTN4	actinin α4	63836	2.46	1.66	−1.48
NFE2L1	nuclear factor, erythroid derived 2,-like 1	360610	2.45	1.29	−1.91
BCL2L1	Bcl2-like 1	24888	2.43	1.88	−1.30
ADAMTS9	metalloprotease with thrombospondin type 1	312566	2.42	2.72	1.12
LOC501282	similar to lymphocyte antigen 6 complex, locus E ligand	501282	2.42	1.47	−1.65
AKT1	v-akt murine thymoma viral oncogene homolog 1	24185	2.41	1.36	−1.78
TIMP2	TIMP metallopeptidase inhibitor 2	29543	2.40	1.60	−1.50
SV2B	synaptic vesicle glycoprotein 2b	117556	2.37	2.71	1.14
SPINT1	serine peptidase inhibitor, Kunitz type 1	311331	2.35	1.56	−1.50

Some gene names were truncated to fit in the table. Genes without annotation were removed from the list. Note that the genes induced by ISO generally showed inhibition in rats exposed to WTC dust (under ISO anesthesia) suggesting likely under-estimation of WTC injury when rats are under anesthesia.

Table 4. Top 30 genes inhibited by isoflurane (ISO) only in lungs of rats (relative to in naïve rats).

Gene symbol	Gene title	Entry gene ID	ISO/Naïve	WTC/Naïve	WTC/ISO
PLUNC	palate, lung, and nasal epithelium associated	246238	−2.48	−2.24	1.11
HPGD	hydroxyprostaglandin dehydrogenase 15 (NAD)	79242	−2.36	−3.02	−1.28
IL1B	IL-1 beta	24494	−1.99	2.00	3.98
MAP2K6	mitogen-activated protein kinase kinase 6	114495	−1.95	−2.30	−1.18
CLCA3	chloride channel calcium activated 3	308015	−1.89	−1.63	1.16
S100A8	S100 calcium binding protein A8	116547	−1.88	2.52	4.73
LRRN3	leucine rich repeat neuronal 3	81514	−1.88	−2.67	−1.42
FMO1	flavin containing monooxygenase 1	25256	−1.82	−2.06	−1.13
BMP4	bone morphogenetic protein 4	25296	−1.78	−1.35	1.33
G0S2	G0/G1switch 2	289388	−1.77	−2.88	−1.63
LRRN1	leucine rich repeat neuronal 1	500280	−1.73	−1.83	−1.06
FLRT3	fibronectin leucine rich transmembrane protein 3	366205	−1.68	−1.67	1.00
MYCN	v-myc myelocytomatosis viral related oncogene	298894	−1.68	−1.32	1.27
IGF1R	insulin-like growth factor 1 receptor	25718	−1.66	−1.07	1.55
TRERF1	transcriptional regulating factor 1	316219	−1.65	−1.69	−1.02
IFIT1	interferon-induced protein with tetratricopeptide repeats 1	56824	−1.65	1.26	2.07
PHLDA1	pleckstrin homology-like domain, family A, member 1	29380	−1.64	1.69	2.77
PPP1R3C	protein phosphatase 1, regulatory (inhibitor) subunit 3C	309513	−1.62	−2.25	−1.39
CCL19	chemokine (C-C motif) ligand 19	362506	−1.62	−1.09	1.49
GIMAP4	GTPase, IMAP family member 4	286938	−1.62	−1.61	1.01
ADORA2A	adenosine A2a receptor	25369	−1.62	−1.53	1.06
NEDD9	neural precursor cell expressed, 9	291044	−1.62	−1.97	−1.22
DSCR6	Down syndrome critical region homolog 6 (human)	288239	−1.60	−1.39	1.15
GCHFR	GTP cyclohydrolase I feedback regulator	171128	−1.59	−1.75	−1.10
NOS2	nitric oxide synthase 2, inducible	24599	−1.56	2.55	3.99
KCNS3	potassium voltage-gated channel, delayed-rectifier, S	83588	−1.56	−1.36	1.15
SIGIRR	single immunoglobulin and toll-interleukin 1 receptor (TIR)	309106	−1.55	−1.21	1.29
EGR1	early growth response 1	24330	−1.54	2.32	3.58
RAB11B	RAB11B, member RAS oncogene family	79434	−1.53	−1.19	1.29
IGJ	immunoglobulin joining chain	360922	−1.52	−1.65	−1.08

Some gene names were truncated to fit in the table. Genes without annotation were removed from the list. Note that many genes inhibited by ISO generally showed increased expression in rats exposed to WTC dust (under ISO anesthesia) suggesting likely under-estimation of WTC injury when rats are under anesthesia.

Figure 2. Heat-map for relative expression of genes involved in inflammatory response in naïve rats and those exposed to only ISO anesthesia or WTC dust (under ISO anesthesia). Genes were clustered using Eisen’s Cluster Analysis with median centering and average linkage. Resulting clusters were visualized with Treeview. Red = genes with higher expression values than median; green = genes with lower expression values than median; black = median expression. Gene list was truncated to fit in the figure and for clarity.

Figure 3. Heat-map for relative expression of genes involved in oxidative stress response in naïve rats and those exposed to only ISO anesthesia or WTC dust (under ISO anesthesia). Genes were clustered using Eisen’s Cluster Analysis with median centering and average linkage. Resulting clusters were visualized with Treeview. Red = genes with higher expression values than median; green = genes with lower expression values than median; black = median expression. Gene list was truncated to fit in the figure and for clarity.