Abstract
Current data suggest that Toll-like receptor 4 (TLR4), a key molecule in the innate immune response, may also be activated following tissue injury. Activation of this receptor is known to induce the production of several proinflammatory cytokines. Given that pulmonary inflammation has been shown to be a key contributor to chronic hypoxia-induced pulmonary vascular remodeling, the authors hypothesized that TLR4-deficient mice would be less susceptible to pulmonary hypertension (PH) as compared to mice with intact TLR4. TLR4-deficient and TLR4-intact strains of inbred mice were exposed to 4, 8, and 16 weeks of hypoxia (0.10 FiO2) or normoxia (0.21 FiO2) in a normobaric chamber. After chronic hypoxic exposure, TLR4-intact mice developed significant PH evidenced by increased right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary artery medial thickening. In contrast, TLR4-deficient mice had no significant change in any of these parameters and this was associated with decreased pulmonary vascular inflammatory response as compared to the TLR4-intact mice. These results suggest that TLR4 deficiency may decrease the susceptibility to developing PH by attenuating the pulmonary vascular inflammatory response to chronic hypoxia.
| Original language | English |
|---|---|
| Pages (from-to) | 111-119 |
| Number of pages | 9 |
| Journal | Experimental Lung Research |
| Volume | 36 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 15 2010 |
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Keywords
- Chronic hypoxia
- Pulmonary hypertension
- Toll-like receptor 4
- Vascular remodeling
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
Toll-like receptor 4deficient mice are resistant to chronic hypoxia-induced pulmonary hypertension. / Young, Karen; Hussein, Sameh M A; Dadiz, Rita; Demello, Daphne; Devia, Carlos; Hehre, Dorothy; Suguihara, Cleide.
In: Experimental Lung Research, Vol. 36, No. 2, 15.03.2010, p. 111-119.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Toll-like receptor 4deficient mice are resistant to chronic hypoxia-induced pulmonary hypertension
AU - Young, Karen
AU - Hussein, Sameh M A
AU - Dadiz, Rita
AU - Demello, Daphne
AU - Devia, Carlos
AU - Hehre, Dorothy
AU - Suguihara, Cleide
PY - 2010/3/15
Y1 - 2010/3/15
N2 - Current data suggest that Toll-like receptor 4 (TLR4), a key molecule in the innate immune response, may also be activated following tissue injury. Activation of this receptor is known to induce the production of several proinflammatory cytokines. Given that pulmonary inflammation has been shown to be a key contributor to chronic hypoxia-induced pulmonary vascular remodeling, the authors hypothesized that TLR4-deficient mice would be less susceptible to pulmonary hypertension (PH) as compared to mice with intact TLR4. TLR4-deficient and TLR4-intact strains of inbred mice were exposed to 4, 8, and 16 weeks of hypoxia (0.10 FiO2) or normoxia (0.21 FiO2) in a normobaric chamber. After chronic hypoxic exposure, TLR4-intact mice developed significant PH evidenced by increased right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary artery medial thickening. In contrast, TLR4-deficient mice had no significant change in any of these parameters and this was associated with decreased pulmonary vascular inflammatory response as compared to the TLR4-intact mice. These results suggest that TLR4 deficiency may decrease the susceptibility to developing PH by attenuating the pulmonary vascular inflammatory response to chronic hypoxia.
AB - Current data suggest that Toll-like receptor 4 (TLR4), a key molecule in the innate immune response, may also be activated following tissue injury. Activation of this receptor is known to induce the production of several proinflammatory cytokines. Given that pulmonary inflammation has been shown to be a key contributor to chronic hypoxia-induced pulmonary vascular remodeling, the authors hypothesized that TLR4-deficient mice would be less susceptible to pulmonary hypertension (PH) as compared to mice with intact TLR4. TLR4-deficient and TLR4-intact strains of inbred mice were exposed to 4, 8, and 16 weeks of hypoxia (0.10 FiO2) or normoxia (0.21 FiO2) in a normobaric chamber. After chronic hypoxic exposure, TLR4-intact mice developed significant PH evidenced by increased right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary artery medial thickening. In contrast, TLR4-deficient mice had no significant change in any of these parameters and this was associated with decreased pulmonary vascular inflammatory response as compared to the TLR4-intact mice. These results suggest that TLR4 deficiency may decrease the susceptibility to developing PH by attenuating the pulmonary vascular inflammatory response to chronic hypoxia.
KW - Chronic hypoxia
KW - Pulmonary hypertension
KW - Toll-like receptor 4
KW - Vascular remodeling
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U2 - 10.3109/01902140903171610
DO - 10.3109/01902140903171610
M3 - Article
VL - 36
SP - 111
EP - 119
JO - Experimental Lung Research
JF - Experimental Lung Research
SN - 0190-2148
IS - 2
ER -