Cystatin B Associates with Signal Transducer and Activator of Transcription 1 in Monocyte-Derived and Placental Macrophages

Luciano-Montalvo, Claribel; Meléndez, Loyda M.

doi:10.1016/j.placenta.2009.03.003

Cited by 28 publications

(41 citation statements)

References 14 publications

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“…They showed that stefin B interacted with several different proteins in HIV-1-infected macrophages, among others also two proteins involved in JAK/STAT signaling pathway [35]. Since stefin B influences the activation of STAT-1 [34] and STAT-3 (our results), we propose that it likely interferes with signaling pathway upstream of STAT-1 and STAT-3. The precise mechanism by which stefin B influences JAK/STAT signaling is yet to be determined.…”

Section: Discussionsupporting

confidence: 52%

Decreased IL‐10 expression in stefin B‐deficient macrophages is regulated by the MAP kinase and STAT‐3 signaling pathways

et al. 2014

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a b s t r a c tInnate immune responses are tightly regulated to avoid excessive activation and subsequent inflammatory damage to the host, and interleukin-10 (IL-10) plays a crucial role in preventing inflammation. Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases. In stefin B-deficient bone marrow-derived macrophages (BMDMs), we detected an increase in the induction of the LPS-induced pro-inflammatory signal nitric oxide (NO) but decreased IL-10 expression. The phosphorylation of ERK and p38 MAP-kinases was significantly decreased in stefin B-deficient macrophages, as was STAT-3 phosphorylation. These findings show that stefin B influences the expression of anti-inflammatory IL-10 in response to the TLR4 agonist LPS.

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Section: Discussionsupporting

confidence: 52%

Decreased IL‐10 expression in stefin B‐deficient macrophages is regulated by the MAP kinase and STAT‐3 signaling pathways

et al. 2014

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“…A recent study found that cystatin B interacts with STAT-1, and tyrosine phosphorylation of this protein was higher in PM. This type of phosphorylation in STAT-1 is associated with decreased HIV transcription [20]. Further studies are needed to elucidate the signaling pathways for the observed restriction in PM.…”

Section: Resultsmentioning

confidence: 99%

Restricted HIV-1 replication in placental macrophages is caused by inefficient viral transcription

Garcia-Crespo

Cadilla

Skolasky

et al. 2009

Journal of Leukocyte Biology

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HIV-infected PM show restricted replication as compared with MDM. We aimed to determine at what point in the viral replication cycle this restriction occurs in PM as compared with MDM. We performed Alu-LTR PCR for proviral DNA to detect differences in HIV integration, real-time RT-PCR to measure env and gag mRNA levels, and Western blot analysis to detect differences in viral protein expression. PM and MDM were infected with HIV-1 BaL, and DNA was extracted after 24 h and at 6 days p.i. for real-time PCR studies. At 6 and 12 days p.i., cells were lysed for Western blot analyses. We found no difference in viral integration between PM and MDM but significantly lower levels of viral protein gp120 in PM than in MDM. Real-time RT-PCR analyses revealed 24-fold less env mRNA and tenfold less gag mRNA in PM. These results suggest that HIV-1 restriction in PM occurs at the level of transcription. This study is significant, as it advances our understanding of HIV-1 infection in PM and its contribution to decreased in utero vertical transmission.

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“…Studies of cathepsin B endogenous inhibitor; cystatin B show the importance of this protein in HIV-1 replication (Luciano-Montalvo and Meléndez 2009; Rivera-Rivera et al 2012) and in other conditions such as progressive myoclonus epilepsy (Lehtinen et al 2009). Our results show increased levels of secreted cystatin B from HIV-infected cocaine-treated MDM cultures compared to cocaine negative HIV infected cultures at 12dpi that parallels with the peak HIV replication.…”

Section: Discussionmentioning

confidence: 99%

Cocaine Potentiates Cathepsin B Secretion and Neuronal Apoptosis from HIV-Infected Macrophages

Zenón

Segarra

Gonzalez

et al. 2014

J Neuroimmune Pharmacol

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Substance abuse is a risk factor for HIV infection and progression to AIDS. Recent evidence establishes that cocaine use promotes brain perivascular macrophage infiltration and microglia activation. The lysosomal protease cathepsin B is increased in monocytes from patients with HIV dementia and its secretion induces 10-15% of neurotoxicity. Here we asked if cocaine potentiates cathepsin B secretion from HIV-infected monocyte-derived macrophages (MDM) and its effect in neuronal apoptosis. Samples of plasma, CSF, and post-mortem brain tissue from HIV positive patients that used cocaine were tested for cathepsin B and its inhibitors to determine the in vivo relevance of these findings. MDM were inoculated with HIV-1ADA, exposed to cocaine, and the levels of secreted and bioactive cathepsin B and its inhibitors were measured at different time-points. Cathepsin B expression (p<0.001) and activity (p<0.05) increased in supernatants from HIV-infected cocaine treated MDM compared with HIV-infected cocaine negative controls. Increased levels of cystatin B expression was also found in supernatants from HIV-cocaine treated MDM (p<0.05). A significant increase in 30% of apoptotic neurons was obtained that decreased to 5% with the specific cathepsin B inhibitor (CA-074) or with cathepsin B antibody. Cathepsin B was significantly increased in the plasma and post-mortem brain tissue of HIV/cocaine users over non-drug users. Our results demonstrated that cocaine potentiates cathepsin B secretion in HIV-infected MDM and increase neuronal apoptosis. These findings provide new evidence that cocaine synergize with HIV-1 infection in increasing cathepsin B secretion and neurotoxicity.

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Cystatin B Associates with Signal Transducer and Activator of Transcription 1 in Monocyte-Derived and Placental Macrophages

Cited by 28 publications

References 14 publications

Decreased IL‐10 expression in stefin B‐deficient macrophages is regulated by the MAP kinase and STAT‐3 signaling pathways

Decreased IL‐10 expression in stefin B‐deficient macrophages is regulated by the MAP kinase and STAT‐3 signaling pathways

Restricted HIV-1 replication in placental macrophages is caused by inefficient viral transcription

Cocaine Potentiates Cathepsin B Secretion and Neuronal Apoptosis from HIV-Infected Macrophages

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