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Updated: Feb 26, 2026
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
CD44 is critical for TLR4-mediated NLRP3 inflammasome activation and the development of bronchopulmonary dysplasia
Jie Liao1, Christopher Longoria1, C Vivek Lal2
1The Center for Pulmonary and Vascular Biology and The Division of Neonatal-Perinatal Medicine, The Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, United States.
Insights
CD44 receptor is crucial in Bronchopulmonary Dysplasia (BPD) pathogenesis. Blocking CD44 activation may prevent BPD by inhibiting NLRP3 inflammasome activation and lung inflammation.
Area of Science:
- Pulmonary Medicine
- Immunology
- Neonatology
Background:
- Bronchopulmonary Dysplasia (BPD) is a chronic lung disease in preterm infants.
- The NLRP3 inflammasome is critical in BPD pathogenesis.
- The role of the hyaluronan receptor CD44 in BPD remains unclear.
Purpose of the Study:
- To investigate the contribution of CD44 to NLRP3 inflammasome activation.
- To determine the role of CD44 in the development of BPD.
Main Methods:
- Utilized CD44 and TLR4 knockout mice models.
- Studied NLRP3 inflammasome activation and BPD development.
- Administered LPS to assess TLR4-specific responses.
Main Results:
- Neonatal hyperoxia increased lung CD44 expression.
- CD44 knockout mice were protected from hyperoxia-induced BPD.
- CD44 deficiency prevented NLRP3 inflammasome activation and inflammation.
- Increased CD44 expression was observed in experimental and human BPD lungs.
Conclusions:
- CD44 plays a significant role in BPD pathogenesis.
- CD44 is implicated in NLRP3 inflammasome activation.
- CD44 represents a potential therapeutic target for BPD.
Rationale:
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants. We previously established the NLRP3 inflammasome as critical in the pathogenesis of BPD. The hyaluronan receptor CD44 interacts with TLR4 to propagate extracellular signals driving inflammation. The role of CD44 in BPD is unclear.
Objectives:
To determine the contribution of CD44 to NLRP3 inflammasome activation and the development of BPD.
Methods:
The activation of the NLRP3 inflammasome and the development of BPD were studied in CD44 and TLR4 knockout (KO) mice. Lipopolysaccharide (LPS) was used to study TLR4-specific responses.
Measurements And Main Results:
In normal mice, lung CD44 decreased in the first 2 postnatal weeks but increased with exposure to neonatal hyperoxia. CD44 KO mice exposed to hyperoxia were protected from decreased alveolarization and inflammatory responses. Increased IL-1β mRNA and protein and cleaved caspase-1 observed in CD44 wild-type (WT) mice were not seen in CD44 KO mice, indicating a failure to activate the NLRP3 inflammasome. Intraperitoneal LPS resulted in increased plasma IL-1β concentrations in CD44 WT mice, which were decreased in CD44 KO mice. Intratracheal LPS caused a neutrophilic inflammation in CD44 WT lungs, which was absent in CD44 KO mice. TLR4 KO mice were protected from neonatal hyperoxia and showed less lung IL-1β and inflammation. Increased lung CD44 expression was observed in the lungs of preterm baboons developing experimental BPD and in the lungs of preterm-born humans at extended corrected ages.
Conclusions:
Collectively, these data implicate CD44 in the pathogenesis of BPD and identify a novel therapeutic target to limit NLRP3 inflammasome activation.
